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Synovial sarcoma (SS) is a rare and aggressive mesenchymal malignancy driven by a unique chromosomal translocation that generates the expression of the SS18:SSX fusion protein. It occurs at almost any anatomical site and most commonly in young adults. The standard curative treatment for primary SS is a wide surgical resection combined with radiotherapy and/or neoadjuvant chemotherapy. The prognosis of SS varies among patients, with the 5 years survival rate ranging from 50 to 60% in adults and 90% in children. Although patient-derived cell lines are a useful resource for the development of new therapies, only a few are available from public cell banks. Therefore, this study aimed to establish and characterize a novel SS cell line. We successfully established a novel cell line, NCC-SS5-C1, harboring an SS18-SSX1 fusion gene. NCC-SS5-C1 cells demonstrated constant growth and invasion ability. We performed integrative drug screening using eight SS cell lines, including NCC-SS5-C1 cells, and examined the response spectrum of existing anticancer agents. We conclude that NCC-SS5-C1 is a useful resource for studying SS.

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of mesenchymal tumors that arise from the sheath of peripheral nerves. MPNSTs exhibit strong metastatic potential, leading to poor clinical outcomes. The clinical utility of radiation therapy and chemotherapy is marginal with respect to overall survival and effective systematic therapies for MPNSTs are still needed to improve patient outcome. Although patient-derived cell lines are an essential tool for the development of novel therapies, only a limited number of cell lines have been reported and are available from cell banks. Thus, we established the novel MPNST cell line, NCC-MPNST6-C1, using surgically resected MPNST tissue. The NCC-MPNST6-C1 cells retained copy-number alterations similar to those of the original tumors and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro, which reflected the malignant features of the original tumor tissue. While the NCC-MPNST6-C1 cells did not exhibit tumorigenesis in nude mice, their use in drug screening resulted in anti-cancer agents with low IC50 values. Hence, we conclude that the NCC-MPNST6-C1 cell line is a useful resource for the study of MPNSTs.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue sarcoma genetically characterized by the presence of the FUS-CREB3L2 gene fusion. While LGFMS exhibits indolent features during its early stages, the rates of recurrence, metastasis, and death from the disease are high. Presently, the role of FUS-CREB3L2 gene fusions in the unique features of LGFMS is not clear, and there is no modality to improve the clinical outcomes of patients with LGFMS; thus, extensive studies on LGFMS are required. Patient-derived cancer cell lines are critical tools for cancer research. However, no cell line has been established for LGFMS. Here, we aimed to develop a novel cell line for LGFMS and successfully established it using surgically resected tumor tissues. The cells, named NCC-LGFMS1-C1, possessed the same fusion genes as their original tumor and visible copy number variations. The cells had a fibroblastic appearance, formed spheroids when they were seeded in a low-attachment dish, and exhibited constant growth and invasion. Additionally, we demonstrated the feasibility of high-throughput drug screening using these cells. In conclusion, the NCC-LGFMS1-C1 cell line is a useful tool for studying LGFMS.

Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastasizing tumor. GCTB is characterized by the presence of unique giant cells and a recurrent mutation in the histone tail of the histone variant H3.3, which is encoded by H3F3A on chromosome 1. GCTB accounts for ~ 5% of primary bone tumors. Although GCTB exhibits an indolent course, it has the potential to develop aggressive behaviors associated with local recurrence and distant metastasis. Currently, complete surgical resection is the only curative treatment, and novel therapeutic strategies are required. Patient-derived cancer cell lines are critical tools for basic and pre-clinical research. However, only a few GCTB cell lines have been reported, and none of them are available from public cell banks. Therefore, we aimed to establish novel GCTB cell lines in the present study. Using curetted tumor tissues of GCTB, we established two cell lines and named them NCC-GCTB2-C1 and NCC-GCTB3-C1. These cells harbored a typical mutation in histones and exhibited slow but constant growth, formed spheroids, and had invasive capabilities. We demonstrated the utility of these cell lines for high-throughput drug screening using 214 anticancer agents. We concluded that NCC-GCTB2-C1 and NCC-GCTB3-C1 cell lines were useful for the in vitro study of GCTB.

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma (RMS) that has fascicular spindle cell and/or sclerosing morphology. SsRMS has a diverse molecular background and is categorized into three groups: congenital/infantile ssRMS with a gene fusion involving the NCOA2 and VGLL2, ssRMS with the MYOD1 mutation, and ssRMS with no recurrent identifiable genetic alterations. Because ssRMS is a newly defined disease concept of RMS, the optimal treatment methods have not been determined. This results in unfavorable prognosis and consequently signals the urgent need for continuous research. Patient-derived cell lines are essential tools in basic and translational research. However, only two ssRMS cell lines with the MYOD1 mutation have been reported to date. Thus, we established a novel ssRMS cell line named NCC-ssRMS2-C1 using a surgically resected tumor tissue from an adult ssRMS patient. NCC-ssRMS2-C1 cells retained the copy number alterations corresponding to the original tumor and are categorized into the group with no recurrent identifiable genetic alterations. NCC-ssRMS2-C1 cells demonstrated constant proliferation, spheroid formation, and capability for invasion in vitro, reflecting the malignant features of the original tumor tissue. In a drug screening test, ssRMS demonstrated remarkable sensitivity to romidepsin, trabectedin, actinomycin D, and bortezomib. Hence, we conclude that the NCC-ssRMS2-C1 cell line is the first ssRMS cell line which belongs to the group with no recurrent identifiable genetic alterations, and it will be a useful resource in both basic and translational studies for ssRMS.

Synovial sarcoma (SS) is defined as a monomorphic blue spindle cell sarcoma showing variable epithelial differentiation, and is characterized by a specific fusion gene, SS18-SSX. Although SS is rare, it accounts for approximately 8% of all soft tissue sarcomas, which occupies a significant proportion of soft tissue tumors. The prognosis of SS is unfavorable, with 5-year survival rate of 50-60%, and only a few anti-cancer agents are recommended for its treatment. Thus, we need to urgently establish novel treatment methods. Patient-derived cell lines are essential tools in basic research and pre-clinical studies. However, there are only 4 publicly available SS cell lines. Therefore, we established a novel SS cell line, NCC-SS4-C1, using surgically resected tumor tissues of a patient with SS. The cell line maintained the characteristic fusion gene, SS18-SSX1, and copy number alteration, in concordance with the original tumor. The cells also exhibited moderate cell proliferation, invasion ability, and spheroid formation ability. Moreover, a drug-screening test using 4 SS cell lines, including NCC-SS4-C1, demonstrated the significant anti-proliferative effects of ALK and HDAC inhibitors. Thus, we concluded that the NCC-SS4-C1 cell line is a useful tool for basic and pre-clinical studies of SS.

Pleomorphic sarcoma (PS) is a heterogeneous group of malignant mesenchymal tumors without a specific histological lineage of differentiation. PS is genetically characterized by genetic instability and diversity and histologically characterized by morphological pleomorphism. PS is one of the most common soft tissue sarcomas. The only curative treatment for PS is complete surgical resection, in which neoadjuvant radiotherapy is frequently combined. PS demonstrates both local recurrence and metastasis after surgical treatment, and effective systemic chemotherapy has not yet been established. Patient-derived cancer cell lines are critical tools for basic and preclinical studies in the development of chemotherapy. However, only six PS cell lines are available from the public cell bank, and none of them are derived from PS after neoadjuvant radiotherapy, despite the fact that radiotherapy causes changes in the posttreatment cancer genome. Here, we reported a novel cell line of PS from a primary tumor specimen resected after neoadjuvant radiotherapy and named it NCC-PS1-C1. NCC-PS1-C1 cells showed a variety of copy number alterations and pathological mutations in TP53. NCC-PS1-C1 cells demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. The screening of antitumor agents in NCC-PS1-C1 cells showed that bortezomib and romidepsin were effective against PS. In conclusion, we report a novel PS cell line from a primary tumor resected after neoadjuvant radiotherapy. We believe that NCC-PS1-C1 will be a useful tool for the development of novel chemotherapies for PS, especially for recurrent cases after neoadjuvant radiotherapy.

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.

Dedifferentiated liposarcoma (DDLPS) is one of the four subtypes of liposarcomas; it is characterized by the amplification of the 12q13-15 region, which includes MDM2 and CDK4 genes. DDLPS has an extremely high local recurrence rate and is refractory to chemotherapy and radiation, which leads to poor prognosis. Therefore, a novel therapeutic strategy should be urgently established for improving the prognosis of DDLPS. Although patient-derived cell lines are important tools for basic research, there are no DDLPS cell lines available from public cell banks. Here, we report the establishment of a novel DDLPS cell line. Using the surgically resected tumor tissue from a patient with DDLPS, we established a cell line and named it NCC-DDLPS1-C1. The NCC-DDLPS1-C1 cells contained 12q13-15, 1p32, and 1q23 amplicons and highly expressed MDM2 and CDK4 proteins. NCC-DDLPS-C1 cells exhibited constant growth, spheroid formation, aggressive invasion, and tumorigenesis in mice. By screening a drug library, we identified that the proteasome inhibitor, bortezomib, had inhibitory effects on the proliferation of NCC-DDLPS1-C1 cells. We concluded that the NCC-DDLPS1-C1 cell line may serve as a useful tool for basic and pre-clinical studies of DDLPS.

Alveolar soft-part sarcoma is a mesenchymal malignancy characterized by the rearrangement of ASPSCR1 and TFE3 and a histologically distinctive pseudoalveolar pattern. Although alveolar soft-part sarcoma takes an indolent course, its long-term prognosis is poor because of late distant metastases. Currently, curative treatments have not been found for alveolar soft-part sarcoma, and hence, a novel therapeutic strategy has long been required. Patient-derived cell lines comprise an important tool for basic and preclinical research. However, few cell lines from alveolar soft-part sarcoma have been reported in the literature because it is an extremely rare malignancy, accounting for less than 1% of all soft-tissue sarcomas. This study aimed to establish a novel alveolar soft-part sarcoma cell line. Using surgically-resected tumor tissue of alveolar soft-part sarcoma, we successfully established a cell line and named it NCC-ASPS1-C1. The NCC-ASPS1-C1 cells harbored an ASPSCR1-TFE3 fusion gene and exhibited slow growth, and spheroid formation. On the other hand, NCC-ASPS1-C1 did not show the capability of invasion. We screened the antiproliferative effects of 195 anticancer agents, including Food and Drug Administration-approved anticancer drugs. We found that the MET inhibitor tivantinib and multi-kinase inhibitor orantinib inhibited the proliferation of NCC-ASPS1-C1 cells. The clinical utility and molecular mechanisms of antitumor effects of these drugs are worth investigating in the further studies, and NCC-ASPS1-C1 cells will be a useful tool for the in vitro study of alveolar soft-part sarcoma.

Spindle-cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma, characterized by unique pathological features. Although distinctive molecular backgrounds such as frequent mutations in MyoD1 have been reported, optimized therapy has not been fully developed, and further investigations are required. Patient-derived cancer models are critical tools for basic and pre-clinical studies. However, there is no model for ssRMS. Thus, this study aimed to develop a novel cell line from the tumor tissue of a patient with ssRMS. Using surgically resected tissue, we successfully established this cell line, named NCC-ssRMS1-C1. These cells exhibited spindle-shape morphology, consistent with the pathological observations of the original tumor tissue. Genetic studies demonstrated that NCC-ssRMS1-C1 cells retained original copy number alterations and the typical point mutation in MyoD1. Malignant phenotypes such as proliferation, spheroid formation, and invasion were confirmed in vitro by studying NCC-ssRMS1-C1 cells. Upon screening an anti-cancer agent library, sensitivity to conventional chemotherapeutic agents such as actinomycin D was revealed. We conclude that the NCC-ssRMS1-C1 cell line will be a useful resource for basic and pre-clinical studies.

Synovial sarcoma is a rare malignancy of mesenchymal origin, characterized by a chromosomal translocation, t(X;18) (p11.2;q11.2). Wide surgical resection with radiation and cytotoxic chemotherapy is established as a standard treatment; however synovial sarcoma remains a high-grade sarcoma with poor prognosis, and novel anti-cancer agents and immunological approaches are currently being developed. The patient-derived cell line is a critical tool for basic and pre-clinical research. However, only a few patient-derived synovial sarcoma cell lines are publicly available from cell banks. Thus, the aim of this study was to establish and characterize a novel cell line for synovial sarcoma. Using a surgically resected tumor tissue from a 48-year-old female patient, we successfully established a cell line, named NCC-SS3-C1. NCC-SS3-C1 cells harbor an SS18-SSX1 fusion gene and exhibit moderate growth, spheroid formation, and invasion. We examined a range of proliferation-inhibiting effects of small molecule anti-cancer compounds, including FDA-approved anti-cancer drugs, using NCC-SS3-C1 cells, and identified anti-cancer drugs which inhibited the proliferation of NCC-SS3-C1 cells at the low concentration. We concluded that NCC-SS3-C1 would be a useful tool for basic and pre-clinical synovial sarcoma research.

Dedifferentiated liposarcoma (DDLPS) is a highly aggressive subtype of liposarcoma that is morphologically defined as a transition from a well-differentiated lipomatous component to a non-lipogenic one. Curative therapy for DDLPS is complete resection, and the benefits of current systemic chemotherapy remain marginal. Although DDLPS is molecularly characterized by co-amplification of MDM2 and CDK4 (12q14-15) and detailed genomic analyses have been conducted by multiple research groups, the effects of molecular targeted drugs are marginal, and novel therapeutic modalities are required. Although patient-derived cell lines are pivotal for cancer research, no DDLPS cell lines are currently available from public cell repositories. Accordingly, in this study, we established a novel DDLPS cell line, NCC-DDLPS5-C1, using surgically resected tumor tissues from a patient with DDLPS. NCC-DDLPS5-C1 cells exhibited typical gene amplification, overexpression of MDM2 and CDK4, and other DNA copy number alterations. The NCC-DDLPS5-C1 cells were capable of rapid cell proliferation, aggressive invasion, and spheroid formation, but not tumor formation in mice. We reported the utility of NCC-DDLPS5-C1 cells for a drug-response assay to detect anticancer drugs that significantly attenuated cell proliferation. Thus, we concluded that the NCC-DDLPS5-C1 cell line could be a useful resource for the study of DDLPS. Considering the diversity of disease in terms of clinical outcomes, continuous efforts are required to develop more patient-derived cancer models with different clinical and pathological backgrounds.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by a germline mutation of the TP53. The lifetime risk of cancer in individuals with LFS is ≥ 70% for men and ≥ 90% for women. Undifferentiated pleomorphic sarcoma (UPS) is one of the core cancers associated with LFS. UPS is a subtype of undifferentiated soft tissue sarcoma that shows no identifiable line of differentiation. The standard curative treatment for UPS is complete surgical resection. However, local recurrence and distant metastasis to the lung can usually be found after resection of the UPS. Therefore, a novel treatment strategy for patients with UPS is required. Although well characterized, patient-derived tumor cell lines facilitate the high-throughput screening of a large number of drugs, and no sarcoma cell lines derived from a patient with LFS have been registered in public cell banks. Thus, this study aimed to establish a novel, well-characterized UPS cell line from a patient with LFS. From surgically resected UPS tumor tissues, we established the first UPS cell line from a patient with LFS and named it NCC-UPS4-C1. NCC-UPS4-C1 harbored copy number alterations and had the TP53 tumor suppressor gene mutation. The cells exhibited constant cell growth and invasive ability. This well-characterized NCC-UPS4-C1 cell line was then utilized for high-throughput screening of 214 anti-cancer drugs, and two effective drugs were identified. One of the two drugs, romidepsin, was commonly effective for the NCC-UPS1-C1, NCC-UPS2-C1, and NCC-UPS3-C1 cell lines that we previously reported; a potential drug for the treatment of UPS was suggested using well-characterized UPS cell lines. These data indicate that NCC-UPS4-C1, which is the first sarcoma cell line established from a patient with LFS, enables researchers to conduct vigorous preclinical research on UPS.

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of mesenchymal tumors that arise from the sheath of peripheral nerves. MPNSTs exhibit strong metastatic potential, leading to poor clinical outcomes. The clinical utility of radiation therapy and chemotherapy is marginal with respect to overall survival and effective systematic therapies for MPNSTs are still needed to improve patient outcome. Although patient-derived cell lines are an essential tool for the development of novel therapies, only a limited number of cell lines have been reported and are available from cell banks. Thus, we established the novel MPNST cell line, NCC-MPNST6-C1, using surgically resected MPNST tissue. The NCC-MPNST6-C1 cells retained copy-number alterations similar to those of the original tumors and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro, which reflected the malignant features of the original tumor tissue. While the NCC-MPNST6-C1 cells did not exhibit tumorigenesis in nude mice, their use in drug screening resulted in anti-cancer agents with low IC

Undifferentiated pleomorphic sarcoma (UPS), previously termed malignant fibrous histiocytoma, is one of the most aggressive sarcomas with no identifiable line of differentiation. Although the molecular mechanism of oncogenesis in UPS has not been clarified, radiation exposure is considered to be a risk factor in the development of UPS. In the treatment of UPS, surgical treatment remains the most important modality. While chemotherapy is considered in unresectable or metastatic cases, UPS is known to be refractory to conventional chemotherapy, leading to an unfavorable prognosis. To improve the clinical outcome of this condition, novel treatment methods are urgently needed. Patient-derived cell lines are essential tools in preclinical studies. However, owing to the rarity of UPS, only four UPS cell lines are publicly available. Thus, we established a novel UPS cell line, NCC-UPS3-C1, using a surgically resected tumor from a patient with radiation-associated UPS. NCC-UPS3-C1 cells had multiple genomic deletions including the tumor suppressor genes CDKN2A and CDKN2B. NCC-UPS3-C1 cells demonstrated constant growth, spheroid formation, and aggressive invasion ability. We also conducted a screening test using 214 drugs and identified that the histone deacetylase inhibitor, romidepsin, is highly effective on NCC-UPS3-C1 cells. Thus, we concluded that the NCC-UPS3-C1 cell line is a useful tool in preclinical studies for UPS.

CIC-DUX4 sarcoma (CDS), an aggressive soft tissue sarcoma, is characterized by a CIC and DUX4 rearrangement. It has a dismal clinical course and high metastatic rate and shows chemotherapy resistance; therefore, a novel therapeutic strategy is required. Patient-derived cell lines are indispensable tools for basic and preclinical research. However, only a few patient-derived CDS cell lines have been currently reported. Therefore, in this study, we aimed to establish and characterize a novel cell line of CDS. We successfully established the NCC-CDS2-C1 cell line by using surgically resected tumor tissue from a patient with CDS. The NCC-CDS2-C1 cells harbored a CIC-DUX4 fusion gene without insertion and exhibited rapid growth, spheroid formation, and invasion. We screened the antiproliferative effects of small anticancer agent compounds, which included FDA-approved anticancer drugs, on NCC-CDS2-C1 cells in comparison with those on the two previously reported patient-derived CDS cell lines, NCC-CDS1-X1-C1 and NCC-CDS1-X3-C1. The response profile of NCC-CDS2-C1 was similar to but distinct from those of the other cell lines for the small anticancer agent compounds. Therefore, we conclude that the NCC-CDS2-C1 cell line will be a useful tool for basic and preclinical studies of CDS.

Dedifferentiated liposarcoma (DDLPS) is a highly malignant subtype of liposarcoma, with characteristic amplification of MDM2 and CDK4 (12q14-15). It is caused by the dedifferentiation of well-differentiated liposarcoma. DDLPS is refractory to conventional chemotherapy; thus, surgical resection is the primary treatment modality. However, complete resection of DDLPS is difficult because of its deep location, which results in poor prognosis. Therefore, novel systemic chemotherapy is required to improve the clinical outcome. Patient-derived cell lines are important tools in the development of novel chemotherapy. However, there are no DDLPS cell lines available from public cell banks. In this study, we established a novel DDLPS cell line, NCC-DDLPS3-C1, using a surgically resected specimen from a patient with DDLPS. NCC-DDLPS3-C1 cells retained the characteristic gene amplification of MDM2 and CDK4. In addition, other gene amplifications and losses related to the poor prognosis of DDLPS were also observed in concordance with the original tumor. The cells also exhibited rapid cell proliferation, aggressive invasion ability, spheroid formation ability, and tumorigenic ability in nude mice. Furthermore, a drug-screening test showed significant antiproliferative effects of proteasome inhibitors and HDAC inhibitors. Thus, the NCC-DDLPS3-C1 cell line should be a useful tool for the development of novel chemotherapy for DDLPS.

Dedifferentiated liposarcoma (DDLPS) is one of the four subtypes of liposarcomas; it is characterized by the amplification of the 12q13-15 region, which includes MDM2 and CDK4 genes. DDLPS has an extremely high local recurrence rate and is refractory to chemotherapy and radiation, which leads to poor prognosis. Therefore, a novel therapeutic strategy should be urgently established for improving the prognosis of DDLPS. Although patient-derived cell lines are important tools for basic research, there are no DDLPS cell lines available from public cell banks. Here, we report the establishment of a novel DDLPS cell line. Using the surgically resected tumor tissue from a patient with DDLPS, we established a cell line and named it NCC-DDLPS1-C1. The NCC-DDLPS1-C1 cells contained 12q13-15, 1p32, and 1q23 amplicons and highly expressed MDM2 and CDK4 proteins. NCC-DDLPS-C1 cells exhibited constant growth, spheroid formation, aggressive invasion, and tumorigenesis in mice. By screening a drug library, we identified that the proteasome inhibitor, bortezomib, had inhibitory effects on the proliferation of NCC-DDLPS1-C1 cells. We concluded that the NCC-DDLPS1-C1 cell line may serve as a useful tool for basic and pre-clinical studies of DDLPS.

Alveolar soft-part sarcoma is a mesenchymal malignancy characterized by the rearrangement of ASPSCR1 and TFE3 and a histologically distinctive pseudoalveolar pattern. Although alveolar soft-part sarcoma takes an indolent course, its long-term prognosis is poor because of late distant metastases. Currently, curative treatments have not been found for alveolar soft-part sarcoma, and hence, a novel therapeutic strategy has long been required. Patient-derived cell lines comprise an important tool for basic and preclinical research. However, few cell lines from alveolar soft-part sarcoma have been reported in the literature because it is an extremely rare malignancy, accounting for less than 1% of all soft-tissue sarcomas. This study aimed to establish a novel alveolar soft-part sarcoma cell line. Using surgically-resected tumor tissue of alveolar soft-part sarcoma, we successfully established a cell line and named it NCC-ASPS1-C1. The NCC-ASPS1-C1 cells harbored an ASPSCR1-TFE3 fusion gene and exhibited slow growth, and spheroid formation. On the other hand, NCC-ASPS1-C1 did not show the capability of invasion. We screened the antiproliferative effects of 195 anticancer agents, including Food and Drug Administration-approved anticancer drugs. We found that the MET inhibitor tivantinib and multi-kinase inhibitor orantinib inhibited the proliferation of NCC-ASPS1-C1 cells. The clinical utility and molecular mechanisms of antitumor effects of these drugs are worth investigating in the further studies, and NCC-ASPS1-C1 cells will be a useful tool for the in vitro study of alveolar soft-part sarcoma.

Spindle-cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma, characterized by unique pathological features. Although distinctive molecular backgrounds such as frequent mutations in MyoD1 have been reported, optimized therapy has not been fully developed, and further investigations are required. Patient-derived cancer models are critical tools for basic and pre-clinical studies. However, there is no model for ssRMS. Thus, this study aimed to develop a novel cell line from the tumor tissue of a patient with ssRMS. Using surgically resected tissue, we successfully established this cell line, named NCC-ssRMS1-C1. These cells exhibited spindle-shape morphology, consistent with the pathological observations of the original tumor tissue. Genetic studies demonstrated that NCC-ssRMS1-C1 cells retained original copy number alterations and the typical point mutation in MyoD1. Malignant phenotypes such as proliferation, spheroid formation, and invasion were confirmed in vitro by studying NCC-ssRMS1-C1 cells. Upon screening an anti-cancer agent library, sensitivity to conventional chemotherapeutic agents such as actinomycin D was revealed. We conclude that the NCC-ssRMS1-C1 cell line will be a useful resource for basic and pre-clinical studies.

Synovial sarcoma is a rare malignancy of mesenchymal origin, characterized by a chromosomal translocation, t(X;18) (p11.2;q11.2). Wide surgical resection with radiation and cytotoxic chemotherapy is established as a standard treatment; however synovial sarcoma remains a high-grade sarcoma with poor prognosis, and novel anti-cancer agents and immunological approaches are currently being developed. The patient-derived cell line is a critical tool for basic and pre-clinical research. However, only a few patient-derived synovial sarcoma cell lines are publicly available from cell banks. Thus, the aim of this study was to establish and characterize a novel cell line for synovial sarcoma. Using a surgically resected tumor tissue from a 48-year-old female patient, we successfully established a cell line, named NCC-SS3-C1. NCC-SS3-C1 cells harbor an SS18-SSX1 fusion gene and exhibit moderate growth, spheroid formation, and invasion. We examined a range of proliferation-inhibiting effects of small molecule anti-cancer compounds, including FDA-approved anti-cancer drugs, using NCC-SS3-C1 cells, and identified anti-cancer drugs which inhibited the proliferation of NCC-SS3-C1 cells at the low concentration. We concluded that NCC-SS3-C1 would be a useful tool for basic and pre-clinical synovial sarcoma research.

CIC-DUX4 sarcoma (CDS), an aggressive soft tissue sarcoma, is characterized by a CIC and DUX4 rearrangement. It has a dismal clinical course and high metastatic rate and shows chemotherapy resistance; therefore, a novel therapeutic strategy is required. Patient-derived cell lines are indispensable tools for basic and preclinical research. However, only a few patient-derived CDS cell lines have been currently reported. Therefore, in this study, we aimed to establish and characterize a novel cell line of CDS. We successfully established the NCC-CDS2-C1 cell line by using surgically resected tumor tissue from a patient with CDS. The NCC-CDS2-C1 cells harbored a CIC-DUX4 fusion gene without insertion and exhibited rapid growth, spheroid formation, and invasion. We screened the antiproliferative effects of small anticancer agent compounds, which included FDA-approved anticancer drugs, on NCC-CDS2-C1 cells in comparison with those on the two previously reported patient-derived CDS cell lines, NCC-CDS1-X1-C1 and NCC-CDS1-X3-C1. The response profile of NCC-CDS2-C1 was similar to but distinct from those of the other cell lines for the small anticancer agent compounds. Therefore, we conclude that the NCC-CDS2-C1 cell line will be a useful tool for basic and preclinical studies of CDS.