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Emerging chemo- and radiotherapy resistance exacerbated the cancer risk and necessitated novel treatment strategies. Although RNA therapeutics against pro-oncogenic genes are highly effective, tumor-specific delivery remains a barrier to the implementation of this valuable tool. In this study, we report a tryptophan-auxotrophic Salmonella typhimurium strain as an onco-therapeutic delivery system with tumor-targeting ability using 4T1 mice breast-cancer model. The receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is a cancer-specific protein that induces the apoptosis of peripheral lymphocytes and confers tumor immune evasion. We designed a long non-coding antisense-RNA against RCAS1 (asRCAS1) and delivered by Salmonella using a non-antibiotic, auxotrophic-selective, eukaryotic expression plasmid, pJHL204. After in vivo tumor-to-tumor passaging, the JOL2888 (ΔtrpA, ΔtrpE, Δasd + asRCAS1) strain exhibited high sustainability in tumors, but did not last in healthy organs, thereby demonstrating tumor specificity and safety. RCAS1 inhibition in the tumor was confirmed by western blotting and qPCR. In mice, JOL2888 treatment reduced tumor-associated macrophages, improved the T cell population, elicited cell-mediated immunity, and suppressed cancer-promoting genes. Consequently, the JOL2888 treatment significantly decreased the tumor volume by 80%, decreased splenomegaly by 30%, and completely arrested lung metastasis. These findings highlight the intrinsic tumor-targeting ability of tryptophan-auxotrophic Salmonella for delivering onco-therapeutic macromolecules.

To obtain quantitative volumetric data for the Golgi apparatus after ionizing radiation (IR) using super-resolution three-dimensional structured illumination (3D-SIM) microscopy. Normal human retinal pigment epithelial (RPE) cells were irradiated with X-rays (10 Gy), followed by immunofluorescence staining of the Golgi marker RCAS1. 3D-SIM imaging was performed using DeltaVision OMX version 4 and SoftWoRx 6.1. Polygon rendering and spot signal identification were performed using Imaris 8.1.2. Differences between groups were assessed by Welch's t test. RCAS1 signals in untreated cells were located adjacent to nuclei and showed a reticular morphology. Upon IR, the area of RCAS1 signals expanded while retaining the reticular morphology. Polygon rendering imaging revealed that the volume of RCAS1 at 48 h post-IR was greater than that for unirradiated cells (93.7 ± 19.0 μm3 vs. 33.0 ± 4.2 μm3, respectively; P < 0.001): a 2.8-fold increase. Spot signal imaging showed that the number of RCAS1 spot signals post-IR was greater than that for unirradiated cells [3.4 ± 0.8 (× 103) versus 1.3 ± 0.2 (× 103), respectively; P < 0.001]: a 2.7-fold increase. This is the first study to report quantitative volumetric data of the Golgi apparatus in response to IR using super-resolution 3D-SIM microscopy. [ABSTRACT FROM AUTHOR]

Aim: Receptor‐binding cancer antigen expressed on SiSo cells (sRCAS1) is responsible for induction of selective immunosuppression. In addition, preclinical studies have shown that sRCAS1 levels may reflect cancer aggressiveness. The main aim of our study was to analyze pre‐ and post‐treatment levels of sRCAS1 in the sera of patients treated for cervical cancer and to evaluate whether the levels change during treatment and their impact on patient prognosis. Methods: The study included 49 patients suffering from cervical cancer. The early stage cervical cancer patients (14) were treated surgically, while the advanced stage patients (35) underwent radiochemotherapy. Serum sRCAS1 levels were evaluated both before and after intervention with the use of the ELISA method. Results: We have found that median serum sRCAS1 levels of patients before intervention were not significantly different from the levels assessed after intervention. There were also no differences when pre‐ and post‐treatment levels were compared within the group of early and of advanced stage patients. Serum sRCAS1 levels were not influenced by either the histopathological type of the tumor or the methods of treatment. High post‐intervention sRCAS1 levels indicated shortened OS when compared to low sRCAS1 levels. Neither pre‐intervention sRCAS1 levels nor the alteration in sRCAS1 levels during treatment were associated with patient prognosis. In multivariate analysis, post‐treatment sRCAS1 levels and clinical stage of cervical cancer remained as independent predictors of survival. Conclusion: High post‐treatment serum sRCAS1 level in cervical cancer patients seems to be a negative prognostic factor for patient overall survival. [ABSTRACT FROM AUTHOR]

Introduction. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a selective suppressor of the immune response that has been linked to the evasion of immune surveillance by cancer cells. However, the exact prognostic impact of RCAS1 on epithelial ovarian cancer (EOC) has not been fully elucidated. The main aim of our study was to evaluate the influence of RCAS1 immunoreactivity (RCAS1-Ir) in EOC cells and in tumor stroma cells on patient overall survival. We also focused on RCAS1-Ir and the structure of the tumor stroma. Material and methods. RCAS1-Ir was evaluated by means of immunohistochemistry in 67 patients with EOC. We distinguished cytoplasmic and membranous immunoreactivity patterns. Results. We found that high cytoplasmic RCAS1-Ir in cancer cells was associated with more than a two-time shortened period of overall survival. Membranous RCAS1-Ir in cancer cells, as well as in tumor stroma macrophages and fibroblasts, did not correlate with patient survival. RCAS1-Ir in the cytoplasm of cancer cells was positively correlated with the degree of tumor stroma infiltration by fibroblasts and macrophages, but not with RCAS1-Ir in these cells. On the other hand, membranous RCAS1-Ir in cancer cells was positively correlated with RCAS1-Ir in fibroblasts and macrophages, but not with their quantity. Conclusions. Due to their different impacts on patient prognosis and tumor stroma structure, it seems that cytoplasmic and membranous RCAS1-Ir in EOC cells may have different biological functions. [ABSTRACT FROM AUTHOR]

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.

Emerging chemo- and radiotherapy resistance exacerbated the cancer risk and necessitated novel treatment strategies. Although RNA therapeutics against pro-oncogenic genes are highly effective, tumor-specific delivery remains a barrier to the implementation of this valuable tool. In this study, we report a tryptophan-auxotrophic Salmonella typhimurium strain as an onco-therapeutic delivery system with tumor-targeting ability using 4T1 mice breast-cancer model. The receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is a cancer-specific protein that induces the apoptosis of peripheral lymphocytes and confers tumor immune evasion. We designed a long non-coding antisense-RNA against RCAS1 (asRCAS1) and delivered by Salmonella using a non-antibiotic, auxotrophic-selective, eukaryotic expression plasmid, pJHL204. After in vivo tumor-to-tumor passaging, the JOL2888 (Δ trpA , Δ trpE , Δ asd  + asRCAS1) strain exhibited high sustainability in tumors, but did not last in healthy organs, thereby demonstrating tumor specificity and safety. RCAS1 inhibition in the tumor was confirmed by western blotting and qPCR. In mice, JOL2888 treatment reduced tumor-associated macrophages, improved the T cell population, elicited cell-mediated immunity, and suppressed cancer-promoting genes. Consequently, the JOL2888 treatment significantly decreased the tumor volume by 80%, decreased splenomegaly by 30%, and completely arrested lung metastasis. These findings highlight the intrinsic tumor-targeting ability of tryptophan-auxotrophic Salmonella for delivering onco-therapeutic macromolecules., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Author(s).)

Non-Hodgkin lymphoma of Waldeyer's ring constitutes a small percentage of cases of palatine tonsil malignancies and its precise etiology remains unknown. RCAS1 (receptor cancer-binding antigen expressed on SiSo cells) has been demonstrated to be associated with poor prognosis, the development of lymph node metastases and participation in tumor microenvironment remodeling. Our aim is to analyze the potential role of RCAS1 expression in the tumor and tumor microenvironment in the development of early-stage palatine tonsil B-cell lymphomas. We selected 20 patients and analyzed tissue samples from the lymphoma and tumor microenvironment of each patient and from a reference group of 20 patients with chronic tonsillitis. The presence of RCAS1 protein immunoreactivity was demonstrated in 65 % of the examined tissue samples of diffuse large B-cell lymphoma and in 25 % of the analyzed stromata in which it was exhibited by CD68-positive cells identified as macrophages and dispersed throughout the stroma. RCAS1 immunoreactivity in the lymphoma tissue samples remained at a level comparable with that of the reference and was significantly higher in these samples than in those from the stroma. Chronic inflammation of the palatine tonsils thus results in intensive infiltration by various types of immune system cells and in excessive RCAS1 immunoreactivity, both of which confirm the important regulatory role of RCAS1 in the immune response in the mucosa-associated lymphatic tissue of Waldeyer's ring. RCAS1 seems to be involved in creating tumor-induced inflammation in the tumor and its microenvironment. [ABSTRACT FROM AUTHOR]

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape. [ABSTRACT FROM AUTHOR]

Background Receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is derived from uterine adenocarcinoma and can induce apoptosis in lymphocytes, allowing tumor cells to escape from immune surveillance. RCAS1 is reportedly expressed in a membranous pattern on tumor cell or soluble one in serum of patients. The aim of this study was to investigate expression patterns of RCAS1 and the effect on apoptosis in oral squamous cell carcinoma (OSCC) cell lines. Methods In four kinds of OSCC cell lines (HSC-2, HSC-3, SQUU-A, and SQUU-B), RCAS1 mRNAs and proteins were determined by RT-PCR and immunocytochemistry. Membranous RCAS1 was determined by flow cytometry. Culture supernatants were analyzed for detection of soluble RCAS1 by dot blotting and enzyme-linked immunosorbent assay. Apoptotic ability of RCAS1 on the erythroid leukemia cell line K562 with the putative receptor was evaluated by flow cytometry in co-culture with highly metastatic SQUU-B, with knocked-down RCAS1 cells or in a no-cell contact condition. Results RCAS1 mRNA and proteins were expressed in all of OSCC cell lines. Membranous pattern were expressed in all cell lines, while soluble pattern was detected in all supernatants. RCAS1 mRNA, membranous and soluble RCAS1 were significantly seen in SQUU-B more than the other 3 cell lines (P < 0.05). K562 apoptosis was induced in co-culture with each of all cell lines, particularly with SQUU-B. Apoptosis was markedly reduced in co-culture with RCAS1 knockdown cells, but was induced in co-culture without cell contract of SQUU-B. Conclusions Our study suggests that RCAS1 has an apoptotic function via membranous/soluble expression pattern in OSCC cells. RCAS1 may thus affect tumor escape from immune surveillance in OSCC by inducing apoptosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of CD44v6 and RCAS1 and the presence of HPV in cervical cancer tissues, to determine serum RCAS1 levels, and to evaluate these components in correlation with clinicopathologic features and survival., Methods: A total of 52 patients consisting of 28 squamous cell carcinoma (SCC) and 24 adenocarcinoma cases, were studied. RCAS1 and CD44v6 expression was evaluated using immunohistochemical staining. HPV 16 and 18 E6 genes were detected using PCR, and serum RCAS1 concentrations were measured using ELISA. Associations between these factors and clinicopathologic features and survival were analyzed., Results: CD44v6 expression was significantly higher in SCC compared with that in adenocarcinoma (P<0.001). It also showed a significant relation to histologic grade (P<0.001) and tumor size (P=0.03). RCAS1 expression was higher in adenocarcinoma than in SCC (P=0.001), and it showed a borderline relation with histological grade (P=0.057). Overall survival was not significantly different in both CD44v6 and RCAS1 expression; however, FIGO stage (P=0.025) and tumor size (P=0.042) resulted statistically different. The pre-surgical treatment serum RCAS1 levels were not associated with any clinicopathological variables. The presence of HPV 16 E6 was higher in SCC, while the presence of HPV 18 E6 was higher in adenocarcinoma (P<0.001). Detection of HPV 16 E6 was significantly associated with expression of CD44v6. The presence of HPV both HPV 16 E6 and HPV 18 E6 was found in cancer tissues with RCAS1 expression, but without any statistical significance., Conclusion: CD44v6 and RCAS1 expression seems to be involved in tumor proliferation and differentiation, but it is not implicated in the progression and invasion of cervical cancer infected by HPV. Pre-treatment levels of serum RCAS1 in cervical cancer are not a diagnostic and predictive biomarker.

Introduction The presence of the aggressive phenotype of the tumor seems to be indicated by the local infiltration of cancer cells and by the development of metastases in the lymph nodes. This phenotype is related to the intensity of the suppressive profile of the tumor microenvironment. The aim of our study has been to gather information about the expression of both RCAS1 and B7 H4 proteins in the macrophages and fibroblasts present within both the microenvironment of cervical cancer tumors and the cancer cells present on the front of the cancer nest. Methods We analyzed the immunoreactivity levels of such antigens as B7 H4 and RCAS1 in the macrophages and fibroblasts of the cancer microenvironment and within the cancer nest in the tissue samples derived from patients on whom both a radical hysterectomy and a lymphadenectomy had been performed following a diagnosis of uterine cervical carcinoma. These patients were then divided into two subgroups according to the extent of the local and distant advancement of the cancer - that is, according to the FIGO stage and the presence or absence of lymph node metastases. Results RCAS1 immunoreactivity levels on the front of the cancer nest statistically significantly increase according to the FIGO stage or the extent of the local spread of the disease while B7 H4 immunoreactivity levels on the tumor front increase in relation to the extent of the distant spread of the disease or the presence of lymph nodes metastases. Conclusion The intensity of the suppressive profile of the cervical cancer microenvironment indicated by the presence of both RCAS1 and B7 H4 on the front of the tumor and in the macrophages and fibroblasts infiltrating the cancer stroma seems to correlate with the extent of both the local and distant advancement of the disease. [ABSTRACT FROM AUTHOR]

RCAS1 is involved in generating the suppressive profile of the tumor microenvironment that helps cancer cells evade immune surveillance. The status of the cells surrounding the cancer nest may affect both the progression of the cancer and the development of metastases. In cases of ovarian cancer, a large number of patients do not respond to the applied therapy. The patient's response to the applied therapy is directly linked to the status of the tumor microenvironment and the intensity of its suppressive profile. We analyzed the immunoreactivity of RCAS1 on the cells present in the ovarian cancer microenvironment in patients with the disease; these cells included macrophages and carcinoma-associated fibroblasts. Later we analyzed the immunoreactivity levels within these cells, taking into consideration the clinical stage of the cancer and the therapeutic strategy applied, such as the number of chemotherapy regiments, primary cytoreductive surgery, or the presence of advanced ascites. In the patients who did not respond to the therapy we observed significantly higher immunoreactivity levels of RCAS1 within the cancer nest than in those patients who did respond; moreover, in the non-responsive patients we found RCAS1 within both macrophages and carcinoma-associated fibroblasts. RCAS1 staining may provide information about the intensity of the immuno-suppressive microenvironment profile found in cases of ovarian cancer and its intensity may directly relate to the clinical outcome of the disease. [ABSTRACT FROM AUTHOR]

Improvement of diagnostic accuracy for pancreatic cancer in pancreatic disease patients was investigated by examining the combination of three diagnostic methods, i.e., measurements of RCAS1 and CEA levels in pancreatic juice and pancreatic juice cytology. Pancreatic juice was collected from 12 pancreatic cancer (PC) and 26 non-PC patients. RCAS1 and CEA levels were measured by using ELISA. RCAS1 expression on surgically resected tissue was immunohistochemically examined for 2 PC patients. By setting the cutoff level of RCAS1 at 10 U/ml and that of CEA at 18.5 μg/ml, sensitivity of RCAS1 was 42% and that of CEA was 50%. On the other hand, sensitivity and specificity increased from 42% and 85% of RCAS1 alone to 75% and 85% in the examination of RCAS1 + CEA + cytology, and the false-negative rate was also reduced to 25% in this combination. Immunohistochemically, a patient with a high RCAS1 level in pancreatic juice had numerous RCAS1-positive tumor cells in the pancreatic juice. We concluded that RCAS1 and CEA measurements together with cytology in pancreatic juice would be a useful combination method for making a differential diagnosis of PC from non-PC. [ABSTRACT FROM AUTHOR]

Basta P, Galazka K, Mach P, Jozwicki W, Walentowicz M, Wicherek L. The immunohistochemical analysis of RCAS1, HLA-G, and B7H4-positive macrophages in partial and complete hydatidiform mole in both applied therapeutic surgery and surgery followed by chemotherapy. Am J Reprod Immunol 2011; 65: 164-172 The suppressive microenvironment developing around the implantating ovum in normal pregnant women may correlate with the development in cancer patients of a suppressive microenvironment of neoplasmatic cells derived from trophoblasts, such as occurs in molar lesions. Macrophages are suitable candidates for mediating not only the balance of the maternal defensive immune responses to external antigens, but also a tolerance to tumor cells. The aim of our study has been to gain information about the expression of RCAS1, B7H4, and HLA-G within the macrophages present in the microenvironment of the molar lesion. We analyzed the immunoreactivity of such antigens as B7H4, RCAS1, and HLA-G on the macrophages present in tissue samples derived from patients on whom curettage was performed after a diagnosis of molar pregnancy. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. We observed a statistically significant increase in the RCAS1-positive macrophage infiltration within the microenvironment of the molar lesions in patients with partial hydatidiform mole in comparison with those patients who exhibited complete hydatidiform mole. There were no such differences, however, in the infiltration of HLA-G- and B7H4-positive macrophages between the two groups of patients. Additionally, we showed that RCAS1- and HLA-G-positive macrophages are more distinct in those cases of complete molar pregnancy where chemotherapy was necessary after surgical treatment while no such differences with respect to B7H4-positive macrophages were observed. The immune-suppressive endometrial microenvironment represented by suppressive macrophages may have an influence on the clinical course of hydatidiform mole. [ABSTRACT FROM AUTHOR]

Abstract: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a secreted antigen that induces apoptosis in putative receptor-expressing cells, including peripheral lymphocytes and natural killer (NK) cells. RCAS1 expression is associated with aggressive characteristics and poor overall survival for 15 different human malignancies. The putative RCAS1 receptor has not been isolated and the mechanism of RCAS1 apoptosis induction remains unclear. This study explores how RCAS1 is involved in apoptosis initiation. The cell lines SiSo and MCF-7, human uterine carcinoma and breast adenocarcinoma, respectively, both express RCAS1, but RCAS1 secretion is undetectable in MCF-7 cells. SiSo and MCF-7 cells were stimulated to induce RCAS1 ectodomain shedding followed by assessment of RCAS1 expression and secretion. Additionally, the RCAS1 putative receptor-expressing human chronic myelogenous leukemia cell line K562 was co-cultured with SiSo, MCF-7, or soluble RCAS1 to follow RCAS1 secretion in apoptosis initiation. RCAS1 secretion was strongly suppressed by inhibitors of metalloproteases, protein kinase C (PKC)-δ, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK), epidermal growth factor (EGF), and G-protein-coupled receptor (GPCR). K562 apoptosis could be induced only by co-culturing with SiSo or soluble RCAS1. RCAS1 is thus secreted by ectodomain shedding, which may represent a pivotal step in RCAS1-induced apoptosis initiation. [Copyright &y& Elsevier]

Citation Dutsch-Wicherek M. RCAS1, MT, and vimentin as potential markers of tumor microenvironment remodeling. Am J Reprod Immunol 2010; 63: 181–188 A tumor stimulates the remodeling of its microenvironment for its own survival. To protect its own growth and induce angiogenesis, the tumor changes the structure of extracellular matrix and the function of existing cells; it thus chemo-attracts immune system cells altering their function. In our study, we discuss the potential markers of tumor microenvironment remodeling. For instance, RCAS1 is a protein responsible for tumor escape from host immunologic surveillance that additionally seems to be involved in the remodeling of the microenvironment. Another protein, metallothionein, which is both anti-apoptotic and pro-proliferative, is also responsible for modulating the response of immune system cells. Most likely, the expression of this protein by the fibroblasts of tumor microenvironment is related to the remodeled phenotype of these cells because of the tumor influence on cancer-associated fibroblasts. Lastly, vimentin is a protein that would appear to be the marker for the mesenchymal transition of cells from the epithelial phenotype. These cells seem to acquire the mesenchymal phenotype to migrate so that they can facilitate the development of metastases. Interestingly, the expression of vimentin has also been observed in the tumor microenvironment as well and may serve as a marker of a remodeled stroma in the process of facilitating tumor spread. [ABSTRACT FROM AUTHOR]

Citation Tskitishvili E, Nakamura H, Kinugasa-Taniguchi Y, Kanagawa T, Kimura T, Tomimatsu T, Shimoya K. Temporal and spatial expression of tumor-associated antigen RCAS1 in pregnant mouse uterus. Am J Reprod Immunol 2010; 63: 137–143 Problem The tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the inhibition of maternal immune response during pregnancy, and participates in the initiation of labor and placental detachment. The aim of our study was to investigate the expression of RCAS1 protein in the uteri of normal pregnant mice. Method of study Uteri with fetuses were collected from pregnant ICR mice on days 1.5, 3.5, 5.5, 7.5, and 9.5 p.c., and uterine and placental tissues were obtained separately on days 11.5, 13.5, 15.5, and 17.5 p.c. Samples were examined using real-time (RT)-PCR, Western blotting, and immunohistochemical analyses. Results In normal pregnant mice, RCAS1 protein mRNA was significantly increased on day 7.5 p.c. Antigen localization was detected in the placenta, decidua, and fetus. Conclusion The results of this study suggest the importance of day 7.5 p.c. for RCAS1 protein expression in connection with placentation as a possible target for future in vivo studies. [ABSTRACT FROM AUTHOR]

Expression of RCAS1 is significantly associated with clinical prognosis in 15 different types of human cancer. We have previously reported that RCAS1 expression is correlated with a decreasing number of vimentin-positive stromal cells in cervical cancer. Moreover, RCAS1 expression is related to the expression of matrix metalloprotease 1 and laminin 5 and angiogenesis. We examined whether RCAS1 contributes to connective tissue remodeling in epithelial ovarian cancer. RCAS1 expression was studied retrospectively via immunohistochemistry. Samples were obtained from resected tumor tissues from 65 patients with epithelial ovarian cancer. Statistical analysis was done to correlate RCAS1 expression and clinicopathologic variables. The associations between RCAS1 expression and the number of vimentin-positive cells or microvessel density were evaluated. Western blot analysis was also performed to verify the perturbation of vimentin expression in fibroblast L cells, following stimulation by soluble RCAS1. RCAS1 expression was detected in 72.3% (47/65 total cases) and significantly correlated with age and histological subtype. Patients with advanced stage, positive lymph node metastasis, or positive peritoneal cytological results had significantly shorter overall survival rates; however, no significant relationship was detected between RCAS1 immunoreactivity and overall survival. In the connective tissue surrounding tumor cells, the number of cells expressing vimentin significantly decreased in relation to the RCAS1 expression level. The growth of L cells was suppressed after stimulation by soluble RCAS1, and the expression of vimentin was markedly diminished. RCAS1 may contribute to connective tissue remodeling by altering the number of vimentin-positive cells in epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Problem Alterations in RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) expression in the placenta and decidua may be related to the regulation of the process of maternal immune tolerance against fetal antigens. Moreover, it has been demonstrated that the occurrence of the spontaneous beginning of stillbirth is related to a decrease in the placental expression of RCAS1. There are no data currently available on the immune processes in decidua during stillbirth. The aim of this study was to evaluate the RCAS1 immunoreactivity level in decidua and to identify the cytotoxic immune cells present during labor, induced after intrauterine fetal death either with a combination of oxytocin (OT) and prostaglandins or with OT alone; a further objective was to assess the potential impact of these molecular alterations on the effectiveness of stillbirth induction. Methods The immunoreactivity of RCAS1, CD3, CD56, CD69, and CD25 was assessed by immunohistochemistry in 31 decidual samples derived from patients in whom the stillbirth occurred before the onset of labor. Results The RCAS1 immunoreactivity level was higher in a statistically significant manner in decidual tissue samples derived from patients in whom OT alone proved insufficient to induce labor after the diagnosis of intrauterine fetal death but required additionally the use of prostaglandins when compared with samples from women in whom stillbirth was induced successfully with OT alone. However, we did not observe any differences either in CD56 and CD3 positive cell presence or in CD25 and CD69 antigen immunoreactivity in the respective decidua of these two groups of patients. Conclusion The level of RCAS1 in decidua seems to influence the effectiveness of stillbirth induction. [ABSTRACT FROM AUTHOR]

Summary: This study used an immunohistochemical technique to examine the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in 84 specimens of oral squamous cell carcinoma (OSCC), 106 specimens of oral epithelial dysplasia (OED, 32 mild, 44 moderate, and 30 severe OED cases), and 20 specimens of normal oral mucosa (NOM). We found that the mean RCAS1 labeling indices (LIs) increased significantly from NOM (12±5%) through mild OED (31±13%), moderate OED (44±17%), and severe OED (56±18%) to OSCC samples (68±20%, p <0.001). A significant correlation was found between the higher mean RCAS1 LI and OSCCs with larger tumor size (p =0.001), positive lymph node metastasis (p <0.001), or more advanced clinical stages (p <0.001). Positive lymph node metastasis (p =0.0073) and RCAS1 LI≧60% (p =0.048) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Kaplan–Meier curve showed that OSCC patients with a RCAS1 LI≧60% had a significantly poorer cumulative survival than those with a RCAS1 LI<60% (log-rank test, p =0.0113). We conclude that the expression of RCAS1 is an early event in oral carcinogenesis. The RCAS1 LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients. [Copyright &y& Elsevier]

Introduction:Scar deciduosis provides a research model that enables us to assess the impact of decidua on the activity and quality of the immune cells infiltrating this scar tissue. This unique model allows us to examine these processes under conditions excluding the impact of placental cells which, along with decidual cells, control the activity of immune cells under physiological conditions. RCAS1 is a protein responsible for the suppression of the cytotoxic immune response during gestation. The present study evaluates the immunoreactivity level of RCAS1 with respect to immune cell status in the decidua and scar deciduosis. Material and Methods:Immunohistochemical analysis of RCAS1, CD3, CD56, CD25, and CD69 antigen immunoreactivity levels was performed in tissue samples derived from scar deciduosis that developed after a previous cesarean section and were excised during a subsequent cesarean section. The control group consisted of decidua samples derived from cesarean section at term. Results:A statistically significantly higher RCAS1 immunoreactivity level was identified in scar deciduosis tissue samples than in decidua derived from a cesarean section at term. The number of CD56+ cells and immunoreactivity of the CD25 antigen level were observed to be statistically significantly higher in scar deciduosis than in the control group. Conclusion:The presence of an enhanced number of immune cells of higher activity in ectopic decidua during the final step of decidualization seems to be associated with an increase in the immunoreactivity level of RCAS1. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Problem RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) is a membrane protein present also in a soluble form that seems to be responsible for the suppression of the cytotoxic immune response during gestation. The present study evaluates the decidual immunoreactivity level of RCAS1 and the serum level of RCAS1 with respect to the progression of labor at the time of cesarean section. Method of study RCAS1 immunoreactivity was assessed by immunohistochemistry in 47 decidual samples, and the RCAS1 serum level was established in 47 blood serum samples derived from patients on whom cesarean sections were performed. The patients were divided into three groups according to the progression of their labor at the time when the cesarean was performed. Results The highest RCAS1 serum concentration and the highest RCAS1 decidual immunoreactivity were found in patients on whom cesarean sections were performed during advanced labor and were statistically, significantly higher than in cases where cesarean sections were performed without labor or after the spontaneous beginning of labor. Conclusion Alterations in the RCAS1 serum and decidua levels seem to be associated with immune response changes during the progression of labor. [ABSTRACT FROM AUTHOR]

Introduction: Tubal rupture seems to be linked to a disturbance in maternal immune response and trophoblast cell invasion. The immunomodulating activity of endometrial cells is necessary for the coexistence of activated immune cells and endometrial cells. RCAS1 and metallothionein (MT) participate in this process. Material and Methods: Tissue samples derived from fallopian tubes and endometrium were collected during one surgical procedure and divided into three groups: unruptured ectopic pregnancy (EP) without bleeding, unruptured EP with hemorrhage into the peritoneal cavity, and ruptured tubal pregnancy. Immunoreactivity of MT, RCAS1, CD56, CD3, CD69 and CD25 were assessed by immunohistochemical methods. Results: The number of CD3+ and CD56+ cells as well as CD69 antigen immunoreactivity in ruptured tubal mucosa of EP were statistically significantly higher than those measured for unruptured EP without bleeding, while at the same time the number of CD56+ cells in endometrium was statistically significantly lower. The growth of immune cell numbers in tubal mucosa during tubal rupture was not associated with an adequate MT and RCAS1 level. Conclusion: Tubal perforation seems to be linked to a concentration of immune cells and a growth of their activity without an adequate increase of the level of proteins compensating for immune cell response. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the escape of tumor cells from immune surveillance and, at the same time, participates in the inhibition of the maternal immune response during pregnancy. The aim of our study was to investigate the expression of tumor-associated RCAS1 protein in the placenta and amniotic membranes and to assess and compare its concentration in amniotic fluid, maternal and cord blood sera in pregnancies complicated by pre-eclampsia. Samples were obtained from women with pre-eclampsia (N =9), pre-eclampsia with IUGR (N =4), normotensive IUGR (N =7) and healthy term controls (N =25) after delivery. Placentas were studied by immunohistochemistry, Western blot analysis and real-time (RT)-PCR. For assessment of RCAS1 protein concentrations in biological fluids, ELISA was performed. RCAS1 mRNA expression in the placentas of pre-eclamptic patients was significantly lower than in controls (p <0.01). The maternal blood serum RCAS1 protein concentration in the pre-eclampsia cases was also significantly lower than in controls (p =0.0207). The other study groups did not differ significantly. This study reveals the possible role of the RCAS1 protein in the development of pre-eclampsia through an immunological pathway. [Copyright &y& Elsevier]

Abstract: Receptor binding cancer antigen expressed on SiSo cells (RCAS1), a tumor-associated antigen, was expressed in various malignant tissues. It is involved in the tumor immune escape. Here, we reported the evidence that knockdown of RCAS1 expression by RNA interference can recovers T cell growth and proliferation. We designed a small hairpin RNA to knockdown RCAS1 expression in MCF-7 cells effectively. Adding RCAS1 protein resulted in a reduced T cell growth rate, an increased T cell apoptosis ratio, the higher activity of Caspase-3 proteases, and decreased IFN-γ secretion. The suppression of RCAS1 expression effectively recover T cell proliferation, reduce apoptosis and partially reverse the T cell function of IFN-γ secretion. [Copyright &y& Elsevier]

Problem The human tumor-associated receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is considered to play a role in the inhibition of the maternal immune response during pregnancy. The aim of our study was to investigate the expression of RCAS1 protein in the placenta and to compare its concentration in maternal and cord blood sera between normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM). Method of study Samples were obtained from women with GDM ( n = 8), women with type 1 DM ( n = 5), and healthy term controls ( n = 27) after delivery. Placentas were studied by immunohistochemistry, and real-time polymerase chain reaction. For assessment of RCAS1 concentrations in maternal and cord blood sera, enzyme-linked immunosorbent assay was performed. Results The RCAS1 protein mRNA expression in the placentas of patients with GDM was significantly lower than that in the controls ( P = 0.005). The maternal blood RCAS1 protein concentration of the GDM cases was also significantly lower than that in the controls ( P = 0.0411), whereas the cord blood RCAS1 protein concentration was significantly higher in the GDM and type 1 DM groups than in the controls ( P = 0.0311 and P = 0.0192, respectively). Conclusion The present results suggest that RCAS1 protein might have an important role in the development of GDM. [ABSTRACT FROM AUTHOR]

The article focuses on the role played by receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in the regulation of tumor growth through angiogenesis in human uterine cancer, based on study conducted in Japan. The study constructed small interfering ribonucleic acid (siRNA) to target RCAS1. It investigated the correlation between RCAS1 expression and angiogenesis in the transfected cells from nude mice. It found that the introduction of RCAS1-encoding gene increased expression of vascular endothelial growth factors (VEGF).

Problem Pre-eclampsia seems to be related to the disturbance of immune tolerance regulation during pregnancy. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) decidual level alterations were concomitant with changes in immune cell number and activity in decidua. As decidual immunomodulating activity participates in the development of immune tolerance during pregnancy, we aimed to evaluate the immunoreactivity level of decidual RCAS1 with respect to the presence and activity of immune cells. Method of study RCAS1, CD3, CD56, CD69, and CD25 immunoreactivity was assessed by immunohistochemistry in 30 decidual samples derived from patients with severe pre-eclampsia (sPE) and from a healthy control group. Results RCAS1 immunoreactivity was statistically significantly higher in decidual tissue samples derived from patients with sPE tissue than in those derived from healthy patients in whom elective cesarean section at term was performed. A statistically significantly lower number of CD56+ and CD3+ cells and lower immunoreactivity level of CD69 were found in patients with sPE compared with those from the control group. Conclusion The limited immune cells infiltration in decidua during sPE is associated with increase in RCAS1 decidual level. [ABSTRACT FROM AUTHOR]

Problem RCAS1 is a protein responsible for the suppression of cytotoxic immune response during gestation. The present study evaluates the immunoreactivity level of RCAS1 with respect to immune cell status during placental abruption (PA) and retained placental tissue (RPT). Method of study RCAS1, CD3, CD56, CD69 and CD25 immunoreactivity was assessed by immunohistochemistry in 66 decidual samples derived from PA and from RPT. Results RCAS1 immunoreactivity was statistically significantly higher in decidual tissue samples derived from patients with RPT than in those derived from patients with PA. A statistically significantly lower number of CD56+ and CD3+ cells and immunoreactivity level of CD69 were found in patients with RPT, compared to those with PA. Conclusion Placental abruption seems to be associated with excessive accumulation and activity of CD3+ and CD56+ cells in decidua, which processes might, in turn, result from an insufficient RCAS1 decidual level. [ABSTRACT FROM AUTHOR]

Abstract: RCAS1, one of the tumor cell surface antigens, is strongly expressed in aggressive tumors. RCAS1 suppresses the in vitro growth of immune effector cells. We investigated the expression of RCAS1 in 57 gliomas using immunohistochemistry. Furthermore, we examined the association of the RCAS1 expression with the infiltration of tumor infiltrating lymphocyte (TIL). RCAS1 overexpression was significantly correlated with high histological grade and poor prognosis. Reduced infiltration and increased apoptosis of TILs was observed in RCAS1-positive regions. Apoptotsis of TILs appeared to be induced by RCAS1. RCAS1 expression in gliomas may play roles in tumor progression and tumor immune escape. [Copyright &y& Elsevier]

Abstract: HIV-1 infection is known to lead to a massive depletion of CD4+ T cells, and the Fas/FasL and TRAIL/TRAIL-receptor systems have been reported to be one of the mechanisms of CD4+ T cell apoptosis in HIV-1 infection. RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) is also an apoptosis-associated protein that induces apoptosis in receptor positive-cells including T cells, and NK cells. To investigate the role of RCAS1 in HIV-1 infection, we stimulated CD4+ T cells, monocytes, and several cell lines by HIV-Tat protein and thus showed that Tat significantly increased the mRNA transcription levels and the secretion of soluble RCAS1 in CD4+ T cells and monocytes. We also showed that the apoptosis induced by HIV-Tat was blocked by inhibiting the expression of RCAS1, using small interfering RNA (siRNA), which was specific for RCAS1. These results indicate that RCAS1 is one of the mechanisms of CD4+ T cell depletion induced by HIV infection. [Copyright &y& Elsevier]

Background: RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is known to induce apoptosis in its receptor-positive cells. The authors investigated RCAS1 expression in oral squamous cell carcinoma (SCC) and its association with the apoptosis of tumor-infiltrating lymphocytes (TILs). Methods: In 130 patients with oral SCC, the expression of RCAS1 in tumor cells was immunohistochemically examined and the apoptosis of TILs was examined by Terminal Deoxynucleotidyltransferase-mediated dUTP Nick End Labeling (TUNEL) staining. Results: RCAS1 was detected both on the cytoplasm and the membrane of tumor cells in 41 of 130 cases (31.5%). Focusing on the expression at the invasive front interacting with host immune cells, RCAS1 was detected in 22 of 130 cases (16.9%). The percentage of TUNEL-positive TILs in cases with RCAS1-positive SCCs was significantly higher than in cases with RCAS1-negative SCCs ( P < 0.0001). Conclusions: RCAS1 can be expressed on oral SCC cells and may be involved in the tumor escape from the host immune system by inducing the apoptosis of TILs. [ABSTRACT FROM AUTHOR]

Abstract: Advanced Gallbladder cancer has an extremely poor prognosis. We examined a patient with resectable gallbladder cancer with associated lung metastasis. A 64-year-old female patient, diagnosed with gallbladder cancer and a solitary benign lung tumor by imaging, was subjected to extensive cholecystectomy and extrahepatic bile duct resection. After one year, a follow-up CT indicated enlargement of the lung tumor; video-assisted right middle lobectomy was then performed. The lung tumor was diagnosed as a metastasis derived from the gallbladder cancer by pathology and immunohistochemistry. Expression of RCAS1, an independent unfavorable prognostic indicator in gallbladder cancer, was observed in both the gallbladder and lung tumors. However, infiltration of CD8+T cells was only seen in the lung metastatic tumor. She has remained free of any evidence of recurrence in the 10 months and 4 years after the first surgery. The results that metastasis is solitary and infiltrated by CD8+T cells correspond with the present clinical history. [Copyright &y& Elsevier]

Abstract: Objectives: RCAS1 is a membrane protein that plays a role in the maintenance of maternal immune tolerance during pregnancy. The work presented here demonstrates the results of RCAS1 expression in placenta in cases of placental abruption and patients with retained placental tissue during the third stage of labor. Study design: The placenta tissue samples were obtained during vaginal and cesarean delivery (derived from 117 pregnancies). Pregnant women were divided into four groups according to the onset of labor and the time of placental detachment in term labors. The samples were analyzed by the Western blot method. Statistical analysis was performed using the Shapiro–Wilk procedure. The Mann–Whitney test and Student''s t-test were applied to compare the differences between parametric data. Results: The average relative amount of RCAS1 observed in those patients with retained placental tissue was statistically significantly higher than in the patients with placental abruption. Conclusion: The differences observed in placental RCAS1 levels confirm the participation of this protein in the inhibition of maternal immune response during gestation. The present results also indicate that RCAS1 participates in the changes in the maternal immune system that take place during parturition and reinforce its potential involvement in the mechanism of placental abruption. [Copyright &y& Elsevier]

Abstract: Objective. : Endometrium is a specialized organ in which phenomena controlling the level of cell proliferation and apoptosis are marked. The aim of our study was to determine the presence of proteins involved in apoptosis and proliferation: RCAS1, MT and the number of CD56-positive cells and their activity to elucidate their possible role in the development of adenocarcinoma and endometriosis. Materials and methods. : MT, RCAS1, CD56-positivity and CD69 expression were assessed in 55 tissue samples by Western blot and immunohistochemistry methods. Results. : We found that endometrium during secretory menstrual cycle phase is characterized by significantly higher RCAS1 and higher MT expression than in proliferative phase. The number of CD56-positive cells and the CD69 antigen expression was significantly increased. Endometrial adenocarcinoma was characterized by significantly increased RCAS1 expression, while MT expression was comparable to the level found in the secretory phase. The number of CD56-positive cells was significantly decreased and their activity was comparable to the level found in the secretory phase. Endometriosis was accompanied by significantly lower RCAS1 and MT expressions, with lower number of CD-56 positive cells and lower expression of CD69 antigen in comparison to the secretory phase. Conclusions. : The ability of endometrium to determine cytotoxic activity (RCAS1 expression changes) and high protection against DNA damage (MT expression) with concomitant changes in the number of immune cells and their activity, observed in normal endometrium during the menstrual cycle phases seems to be fundamental for pathological features of endometrial adenocarcinoma and endometriosis. [Copyright &y& Elsevier]

Abstract: Objectives.: RCAS1 expression is significantly associated with clinical prognosis in various human cancers, which suggests that RCAS1 may be involved in acquisition of malignant phenotypes. To investigate the relationship between RCAS1 and one such characteristic, tumor invasiveness, we examined RCAS1 expression in cervical neoplasms ranging from the precancerous state to invasive cancer. Methods.: RCAS1 expression was studied retrospectively via immunohistochemical methods. Samples consisted of biopsy tissue from 90 patients with intraepithelial neoplasia and resected tumor tissue from 154 patients with invasive cancer. Statistical analysis was done to correlate RCAS1 expression and clinicopathologic variables in patients with a depth of cancer cell invasion into stromal tissue of >5 mm. Results.: RCAS1 expression was detected in patients with intraepithelial cancer and invasive cancer but not in patients with dysplasia. The occurrence and degree of RCAS1 expression increased with the depth of invasion. In patients with invasive cancer, RCAS1 overexpression was significantly correlated with invasion of the lymph-vascular space, lymph node metastasis in two or more sites, and tumor volume; RCAS1 expression was not associated with histologic subtype. Overall survival rates for patients with RCAS1 overexpression were significantly shorter than those for patients without RCAS1 overexpression. In connective tissue surrounding tumor cells, the number of cells expressing vimentin significantly decreased in relation to RCAS1 expression level. Moreover, significant associations between expression levels of RCAS1 and those of MMP-1 and laminin-5 were found. Conclusion.: RCAS1 may contribute to acquisition of malignant uterine cervical phenotypic characteristics including invasion, metastasis, and tumor growth via connective tissue remodeling. [Copyright &y& Elsevier]

Since receptor-binding cancer antigen expressed on SiSo cells (RCAS1) was first reported as a tumor-associated antigen of gynecologic cancer, its function and practical value as a tumor marker have been investigated in various types of carcinomas. Basic research has indicated that RCAS1 expression in cancer cells contributes to the evasion from immune surveillance and progression of carcinomas. The clinical significance of RCAS1 expression in hepatobiliary and pancreatic carcinomas has also been investigated. In this review, we summarize the clinical application of RCAS1 antigen in hepatic and pancreaticobiliary diseases. We present new data and review current knowledge about the potential of RCAS1 as a tumor marker and the relationship between RCAS1 expression and clinicopathologic parameters. We found that the clinical function of RCAS1 appeared to differ according to the type of carcinoma. In hepatocellular carcinoma, the clinical significance of histological RCAS1 expression was controversial and that of serum RCAS1 levels showed little clinical value. In pancreaticobiliary cancers, high RCAS1 expression in tissue samples was an unfavorable independent prognostic factor. Serum RCAS1 was a superior tumor marker reflecting the disease activity in biliary carcinoma. In pancreatic cancer, serum RCAS1 levels were less useful than in biliary carcinoma but may be available for genetically CA19-9-negative patients and for CA19-9-non-producing cancer. This review also offers suggestions for future studies. [ABSTRACT FROM AUTHOR]

Abstract: Objective. : The presence of regional lymph node metastasis is one of the prognostic factors for uterine cervical cancer. The development of metastasis requires that cancer cells avoid lymphocyte attack. Impaired lymphocyte function is mediated by apoptotic factors including receptor-binding cancer antigen expressed on SiSo cells (RCAS1), Fas ligand (FasL), and tumor necrosis factor-α (TNF-α). Our aim was to evaluate the association between expression of these factors and microenvironmental lymphocyte apoptosis in this disease. Methods. : Immunohistochemical methods were used to determine the relationship between the expression of RCAS1, FasL, and TNF-α, and the number of apoptotic lymphocytes in primary lesions and metastatic lymph nodes in patients with cervical cancer. Results. : Expression of these apoptosis-inducing molecules was quite different in primary tumors and metastatic lymph nodes: RCAS1 expression in lymph nodes was significantly higher than that in primary lesions (P &#60; 0.0001), whereas FasL and TNF-α expressions at these two locations were not significantly different. The number of cells with positive expression of RCAS1, but not of FasL or TNF-α, was significantly correlated with the number of apoptotic lymphocytes in uterine cervix and metastatic lymph nodes (P &#60; 0.0001 for both). Conclusion. : RCAS1 expression may be related to tumor cell evasion of immune surveillance via induction of lymphocyte apoptosis in primary lesions and metastatic lymph nodes in uterine cervical cancer. [Copyright &y& Elsevier]

Suehiro Y, Muta K, Nakashima M, Abe Y, Shiratsuchi M, Shiokawa S, Ikuyama S, Yoshikawa Y, Watanabe T, Nishimura J. A novel mechanism in suppression of erythropoiesis during inflammation: a crucial role of RCAS1.Eur J Haematol 2005: 74: 365–373.© Blackwell Munksgaard 2005.A novel human tumor-associated antigen, receptor-binding cancer antigen expressed on SiSo cells (RCAS1), induces apoptosis in normal human erythroid progenitor cells, which express putative RCAS1 receptors. In the present study, we investigated a possible role of RCAS1 produced by human peripheral blood monocytes (CD14-positive cells) and monocyte-derived macrophages. RCAS1 was immunohistochemically detected in monocytes as well as macrophages. When macrophages were stimulated with lipopolysaccharide (LPS), the expression of RCAS1 was remarkably enhanced. An increased production of RCAS1 mRNA was observed in LPS-stimulated macrophages by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Soluble RCAS1 molecules were only detected in the culture supernatants obtained from LPS-stimulated macrophages. Moreover, LPS-stimulated macrophages induced cell death of erythroid progenitor cells through RCAS1 production. These results suggest that macrophages may negatively regulate erythropoiesis at least in part through the production of RCAS1 molecules, and this may contribute to the pathogenesis of the anemia seen in patients with inflammatory disorders. [ABSTRACT FROM AUTHOR]

Background/Aims: The tumor-associated antigen, RCAS1, has been reported to be expressed in various types of cancer, including cholangiocarcinoma. We measured serum RCAS1 levels in patients with intrahepatic cholangiocellular carcinoma (CCC) and other hepatobiliary diseases, and examined the clinical significance of serum RCAS1 as a tumor marker.Methods: Sera collected from the patients and healthy volunteers were used for ELISA for RCAS1. The values of RCAS1 for CCC patients were compared to those of other tumor marker proteins.Results: Serum RCAS1 levels exceeded the normal limit in a high percentage (73.9%) of CCC patients. The positivity rate was higher than those of CA19-9 and CEA. No correlation was found between the RCAS1 and CA19-9 concentrations. Serum RCAS1 was positive in many cases that were negative for CA19-9. Surgical resection of CCC reduced the RCAS1 level to within the normal range. On the other hand, serum RCAS1 levels were elevated in very few cases of benign hepatobiliary disease.Conclusions: As a tumor marker in CCC, RCAS1 is, at least, of complementary value to CA19-9 and CEA. Measuring serum RCAS1 contributes to the diagnostic accuracy, and is useful for estimating tumor progression or therapeutic effect. [Copyright &y& Elsevier]

Objective: Counterattack by RCAS1 on carcinoma to cytotoxic T cells and natural killer (NK) cells has been suggested as a contribution to carcinoma progression, because RCAS1 can inhibit their proliferation and induce apoptosis. In this study, we examined RCAS1 expression in various thyroid neoplasms in order to clarify its clinical significance. Methods: We studied RCAS1 expression by means of immunohistochemistry using a mouse monoclonal antibody against RCAS1 for normal thyroid epithelium, follicular adenoma, follicular carcinoma, papillary carcinoma and undifferentiated (anaplastic) carcinoma. Results: Normal epithelium and follicular adenoma did not express or only faintly expressed RCAS1. In thyroid carcinomas. RCAS1 overexpression was more frequently observed in anaplastic (undifferentiated) carcinomas than papillary (p < 0.0001) and follicular carcinomas (p = 0.0018). In follicular carcinoma, the widely invasive type more frequently overexpressed RCAS1 than the minimally invasive type (p = 0.0488). Furthermore, the incidences of RCAS1 overexpression increased with carcinoma dedifferentiation (p < 0.0001). Conclusion: These results suggest that RCAS1 may contribute to the progression of thyroid carcinoma with high biological aggressiveness.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the prognostic value of receptor binding cancer antigen expressed on SiSo cells (RCAS1) expression and host immune response in gastric carcinomas. Methods: We investigated the relationship between RCAS1 expression, density of tumor-infiltrating lymphocytes (TIL), and clinicopathological findings in 129 patients with T3 gastric carcinoma who underwent curative surgery. Results: RCAS1 immunoreactivity was detected in the membrane and cytoplasm of tumor cells. Positive immunoreactivity for RCAS1 was detected in 70 patients (54.3%) and high expression levels of RCAS1 were found in 33 patients (25.6%). The expression of RCAS1 significantly correlated with the histological type of carcinoma and lymph node metastasis. Apoptotic rates in TILs showed marginally higher significance in patients with high RCAS1 expression than in those with low expression. The 5-year survival rates were 77.9% in patients with low RCAS1 expression and 48.4% in those with high RCAS1 expression. Although there was no significant difference in survival between the patients with marked and slight infiltration of TILs, frequent apoptosis in TILs indicated significantly worse prognosis. Patients with low RCAS1 expression survived significantly longer than those with high RCAS1 expression, as did those patients with a high rate of apoptosis in TILs. Multivariate analysis revealed that RCAS1 expression, as well as tumor size and lymph node metastasis, was an independent prognostic factor. Conclusions: The expression of RCAS1 was significantly correlated with poor prognosis in patients with T3 gastric carcinoma. RCAS1 protein may play an important role in the evasion of tumor cells from immunological defense mechanisms in human gastric carcinoma. [ABSTRACT FROM AUTHOR]

Background/Aims: RCAS1, which is recognized by the specific antibody 22-1-1, was first identified as a tumor-associated antigen in gynecological carcinomas. RCAS1 is the ligand of a putative receptor present on lymphocytes, the expression of which is enhanced by lymphocyte activation. RCAS1 inhibits the growth of receptor-bearing cells and induces apoptotic death. Here we examined RCAS1 expression in biliary diseases.Methods: RCAS1 expression was immunohistochemically examined on tissue samples. Apoptotic death was analyzed by DNA fragmentation detection method. RCAS1 production by cell lines was investigated by flow cytometry, enzyme-linked immunosorbent assay, and reverse transcription–polymerase chain reaction.Results: All cholangiocarcinoma cell lines examined clearly expressed RCAS1 at both the protein and RNA level. Immunohistochemically, RCAS1 was expressed in a high percentage of biliary adenocarcinomas (85.9% of intrahepatic cholangiocarcinomas, 96.4% of extrahepatic cholangiocarcinomas and gallbladder carcinomas). Apoptotic tumor-infiltrating lymphocytes could be found in these specimens. RCAS1 expression was frequently detected also in biliary epithelial cells in cases of immune-mediated cholangitis (74.2% in primary biliary cirrhosis, 66.6% in graft-versus-host disease), although the staining pattern for RCAS1 was different compared with cancer cells.Conclusions: RCAS1 is highly expressed not only in cancer cells but also in non-tumor bile duct cells subjected to immune attack. [Copyright &y& Elsevier]

RCAS1/EBAG9 (receptor-binding cancer antigen expressed on SiSo cells/ estrogen receptor-binding fragment-associated gene 9), an estrogen-transcribed protein, has been shown to be expressed in a wide variety of cancers, including uterine, ovarian, and lung cancer cells. Soluble and membranous RCAS1 proteins may play a role in the immune escape of tumor cells by promoting T lymphocyte inhibition of growth and apoptosis. In the present report, the presence of RCAS1 was revealed in human ductal breast cancer biopsies by immunohistochemistry. Its cytoplasmic expression was exhibited in cancer cells obtained from tumor biopsies and in breast cancer cell lines. RCAS1 significantly correlated with tumor grade. In addition, RCAS1 was identified in MCF7 culture supernatants. Those observations suggest that RCAS1 is a new marker for breast cancer progression and a possible mechanism for breast cancer immune escape. [Copyright &y& Elsevier]

Objective: RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a new tumor-associated antigen recognized by 22-1-1 monoclonal antibody. RCAS1 expressed on human cancer cells acts as a ligand for a putative receptor present on peripheral lymphocytes. RCAS1 has been shown to inhibit the in vitro growth of receptor-expressing cells and to induce apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we evaluated the prognostic significance of RCAS1 expression in primary lung adenocarcinomas. Methods: Immunohistochemical analysis was performed on tissue specimens surgically obtained from 102 patients with primary lung adenocarcinomas. Then, the association of RCAS1 expression with clinicopathological variables and prognosis of patients were analyzed. Results: Of 102 lung adenocarcinomas, positive RCAS1 expression was observed in 82 cases (80%). There was no correlation between RCAS1 expression and clinicopathological variables. In 70 potentially curatively resected lung adenocarcinomas, patients with RCAS1-positive tumors had a significantly shorter survival than those with RCAS1-negative tumors (p = 0.02), and RCAS1 expression was a significant and independent prognostic factor by multivariate analysis (p = 0.03). Conclusions: These results indicate that RCAS1 expression predicts prognosis in patients with lung adenocarcinomas, and this new antigen could be a novel tumor marker which reflects the clinical outcome of lung cancers.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Overexpression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) protects cancer cells from immune attack and might be related to poor prognosis in several cancers. We investigated the immunoreactivity of RCAS1 and its correlation with clinicopathological features in 95 patients who underwent surgical resection for oesophageal squamous cell carcinoma. Thirty-two of the 95 (33.7%) cases were strongly positive for RCAS1. RCAS1 showed significant correlations with age and stage grouping. Expression of RCAS1 was associated with shorter postoperative survival. Multivariate analysis indicated that RCAS1 positivity was an independent negative prognostic factor. Our study establishes RCAS1 as a novel prognostic marker for surgically resected oesophageal squamous cell carcinoma. [Copyright &y& Elsevier]