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Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, presents a significant challenge because of its high recurrence rate, distal metastasis, and complex genetic background. Although surgical resection is the standard treatment for MFS, the outcomes are unsatisfactory and effective non-surgical treatment strategies, including drug therapy, are urgently warranted. MFS is a rare tumor that requires comprehensive preclinical research to develop promising drug therapies; however, only two MFS cell lines are publicly available worldwide. The present study reports two novel patient-derived MFS cell lines, NCC-MFS7-C1 and NCC-MFS8-C1. These cell lines have been extensively characterized for their genetic profile, proliferation, spheroid-forming capacity, and invasive behavior, confirming that they retain MFS hallmarks. Furthermore, we conducted comprehensive drug screening against these cell lines and six others previously established in our laboratory to identify potential therapeutic candidates for MFS. Among the screened agents, actinomycin D, bortezomib, and romidepsin demonstrated considerable antiproliferative effects that were superior to those of doxorubicin, a standard drug, highlighting their potential as novel drugs. In conclusion, NCC-MFS7-C1 and NCC-MFS8-C1 are valuable research resources that contribute to the understanding of the pathogenesis and development of novel therapies for MFS., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Synovial sarcoma (SS) is identified as a sarcoma with monomorphic blue spindle cells that display variable epithelial differentiation and is characterized by the SS18::SSX fusion gene. SS accounts for approximately 5-10% of all soft tissue sarcomas, making it a relatively common type within this group of tumors. Since SS is generally sensitive to chemotherapy, the standard treatment for SS includes extensive surgical resection, complemented by neoadjuvant chemotherapy with several approved anticancer drugs. However, in advanced and metastatic cases, the efficacy of these drugs is limited, resulting in poor prognoses. This underscores the need for innovative therapeutic strategies. Patient-derived cancer cell lines are essential tools for basic and preclinical research, yet only four SS cell lines are publicly available. To facilitate the studies of SS, we have developed a novel SS cell line, named NCC-SS6-C1, derived from surgically excised tumor tissue of an SS patient. NCC-SS6-C1 cells preserve the SS18::SSX1 fusion gene, consistent with the genetic characteristics of the original tumor. The cells exhibit continuous proliferation, invasiveness, and the ability to form spheroids. Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by rearrangement of the ASPSCR1 and TFE3 genes and a histologically distinctive pseudoalveolar pattern. ASPS progresses slowly, but is prone to late metastasis. As ASPS is refractory to conventional chemotherapy, the only curative treatment is complete surgical resection. The prognosis of advanced and metastatic cases is poor, highlighting the need for preclinical research to develop appropriate treatment options. However, ASPS is extremely rare, accounting for < 1% of all soft tissue sarcomas, and only one patient-derived ASPS cell line is available from public cell banks worldwide for research. This study reports the establishment of a novel ASPS cell line derived from the primary tumor tissue of an ASPS patient, named NCC-ASPS2-C1. This cell line retains the ASPSCR1-TFE3 fusion gene, which is characteristic of ASPS. The characterization of this cell line revealed stable growth, spheroid formation, and invasive properties. By screening a drug library using NCC-ASPS2-C1, we identified several drugs that inhibited the proliferation of ASPS cells. In conclusion, the establishment of NCC-ASPS2-C1 provides a valuable resource for advancing ASPS research and developing novel treatments for this challenging disease., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Dermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP cell lines are currently available in public cell banks. Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation and maintain the same mutation as the original tumor tissue. They exhibited consistent growth, formed spheroids, and were invasive. By screening a drug library using NCC-DFSP5-C1 and four previously established DFSP cell lines, we identified anti-cancer drugs that inhibit DFSP cell proliferation. Our observations suggest that the NCC-DFSP5-C1 cell line holds promise as a valuable tool for conducting fundamental and preclinical studies for DFSP., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy, which originates from the smooth muscle cells or from the precursor mesenchymal stem cells that potentially differentiate into smooth muscle cells. LMS is one of the most common sarcomas. LMS has genomic instability, reflecting complex and unbalanced karyotypes, and the cytogenetic and molecular changes in LMS are not consistent. The standard treatment of the primary LMS is complete resection, and the metastasis is often observed even after curative surgery. Patient-derived cancer models are a key bioresource to develop a novel therapy, and we aimed to establish and characterize a novel cell line for LMS. We established a cell line from tumor tissues of the patient with LMS and named it NCC-LMS3-C1. We maintained NCC-LMS3-C1 cells for 12 months and passed them more than 30 times. Genome-wide copy number analysis demonstrated that NCC-LMS3-C1 cells harbored genetic abnormalities. NCC-LMS3-C1 cells exhibited aggressive phenotypes such as continuous growth, spheroid formation, and invasion in the tissue culture condition, which may reflect the clinical behaviors of LMS. We performed a drug screening using NCC-LMS3-C1 cells and found that four anti-cancer agents, such as bortezomib, dasatinib, mitoxantrone, and romidepsin, had remarkable anti-proliferative effects on NCC-LMS3-C1 cells. We conclude that NCC-LMS3-C1 cells will be a useful resource for the study of LMS., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Dermatofibrosarcoma protuberans (DFSP) is a superficial low-grade sarcoma, genetically characterized by a fusion gene in collagen type I α (COL1A1) gene and platelet-derived growth factor subunit β (PDGFB). DFSP is locally aggressive and does not typically metastasize. However, DFSP with fibrosarcomatous transformation, which occurs in 7-16% of DFSP cases, demonstrates a poor prognosis than classic DFSP with a higher local recurrence rate and metastatic potential. Although imatinib, a PDGF receptor inhibitor, is a potent therapeutic agent for classic DFSP, it is less effective for DFSP with fibrosarcomatous transformation. The development of definitive chemotherapies for DFSP with fibrosarcomatous transformation is required. Patient-derived tumor cell lines are indispensable tools for preclinical research to discover novel therapeutic agents. However, only seven cell lines were derived from DFSP, out of which only two were established from DFSP with fibrosarcomatous transformation. Hence, in the present study, we established a novel DFSP cell line, NCC-DFSP4-C1, from a surgically resected DFSP tumor specimen with fibrosarcomatous transformation. NCC-DFSP4-C1 harbored an identical COL1A1-PDGFB fusion gene as its donor tumor. NCC-DFSP4-C1 cells retained the morphology of their donor tumor and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. By screening a drug library, we found that bortezomib and romidepsin demonstrated the strongest suppressive effects on the proliferation of NCC-DFSP4-C1 cells. In conclusion, we report a novel cell line of DFSP with fibrosarcomatous transformation, and demonstrate its utility in the development of novel therapeutic agents for DFSP., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Giant cell tumor of bone (GCTB) is a rare bone tumor with osteolytic features, composed of stromal cells with a monotonous appearance, macrophages, and osteoclast-like giant cells. GCTB is commonly associated with a pathogenic mutation in the H3-3A gene. While complete surgical resection is the standard cure for GCTB, it often results in local recurrence and, rarely, metastasis. Thus, an effective multidisciplinary treatment approach is necessary. Although patient-derived cell lines is an essential tool for investigating novel treatment strategies, there are only four GCTB cell lines available in public cell banks. Therefore, this study aimed to establish novel GCTB cell lines and successfully created NCC-GCTB6-C1 and NCC-GCTB7-C1 cell lines from two patients' surgically removed tumor tissues. These cell lines exhibited H3-3A gene mutations, consistent proliferation, and invasive properties. After characterizing their behaviors, we performed high-throughput screening of 214 anti-cancer drugs for NCC-GCTB6-C1 and NCC-GCTB7-C1 and integrated their screening data with those of NCC-GCTB1-C1, NCC-GCTB2-C1, NCC-GCTB3-C1, NCC-GCTB4-C1, and NCC-GCTB5-C1 that we previously established. We identified histone deacetylase inhibitor romidepsin as a possible treatment for GCTB. These findings suggest that NCC-GCTB6-C1 and NCC-GCTB7-C1 could be valuable tools for preclinical and basic research on GCTB., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Desmoid fibromatosis (DSM) is a rare, locally aggressive mesenchymal tumor genetically characterized by mutations in the CTNNB1 gene. A local control rate of up to 65‒80% for DSM is achieved with multiple modality treatments, including watchful monitoring, radiation therapy, chemotherapy, and surgery. However, several variables, such as age < 30 years, extremity tumor location, and tumor size of > 10 cm in diameter, are associated with poor local control rates in patients with DSM. The definitive treatments for DSM have not been established. Therefore, it is necessary to develop novel treatments for DSM. Moreover, although patient-derived tumor cell lines are potent tools for preclinical research, no DSM cell lines have been reported. Therefore, this study aimed to establish and characterize a novel DSM cell line for preclinical studies on DSM. Herein, we established the first cell line derived from a patient with DSM exhibiting poor prognostic factors (27-year-old male patient with a DSM tumor of > 10 cm in diameter located at the lower extremity) and named it NCC-DSM1-C1. NCC-DSM1-C1 cells had a T41A mutation in CTNNB1 and exhibited constant proliferation, spheroid formation, and invasion capability in vitro. Screening of antitumor agents in NCC-DSM1-C1 cells showed that bortezomib and romidepsin are effective against DSM. In conclusion, we report the first officially characterized DSM cell line derived from a patient with DSM exhibiting factors associated with poor prognosis. We believe that NCC-DSM1-C1 cell line is a useful tool for developing novel treatments for DSM., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Pleomorphic liposarcoma (PLPS) is a highly malignant subtype of liposarcoma. It is histologically characterized by the presence of pleomorphic lipoblasts and can be accompanied by morphological foci that demonstrate differentiation to other histological lineages. PLPS is rare and accounts for only 5% of all liposarcomas. PLPS exhibits poor prognosis; distant metastases develop in 30-50% of patients after curative surgical resection, tumor-associated mortality occurs in up to 50% of patients, and effective chemotherapies for PLPS have not been established. The histological accompaniment of other morphological foci is an important prognostic factor for PLPS, and the development of chemotherapies for PLPS considering the histological morphology is necessary. Patient-derived cancer cell lines are critical tools for basic and pre-clinical research to understand diseases and develop chemotherapies. However, only two PLPS-derived cell lines have been reported, and their donor tumor specimens did not histologically accompany morphological foci other than lipoblasts. Thus, there is a need to establish patient-derived PLPS cell lines from various histological morphologies. Here, we report a novel PLPS cell line from a tumor specimen that histologically accompanied pleomorphic and bone-forming foci, and named it NCC-PLPS2-C1. NCC-PLPS2-C1 cells demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. Screening of antitumor agents in NCC-PLPS2-C1 cells showed that bortezomib, romidepsin, and trabectedin were effective against NCC-PLPS2-C1. In conclusion, we report the first PLPS cell line from a tumor specimen that was morphologically accompanied by pleomorphic and born-forming foci. We believe that NCC-PLPS2-C1 will be useful for the development of novel chemotherapies for PLPS., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Malignant rhabdoid tumor (MRT) is a sarcoma histologically characterized by rhabdoid cells and genetically characterized by loss of function of the chromatin remodeling complex SWI/SNF induced by SMARCB1 gene deficiency. MRT mainly occurs in children, may arise in various locations, but is predominantly in the central nervous system (CNS) and kidney. Although MRT exhibits poor prognosis, standard treatment has not yet been established due to its extreme rarity. Patient-derived cancer cell lines are critical tools for basic and pre-clinical research in the development of chemotherapy. However, none of the MRT cell lines was derived from adult patients, and only one cell line was derived from the MRT of a soft tissue, despite the clinical behavior of MRT varying according to patient age and anatomic site. Herein, we reported the first cell line of MRT isolated from the soft tissue of an adult patient and named it NCC-MRT1-C1. NCC-MRT1-C1 cells showed a biallelic loss of the SMARCB1 gene. NCC-MRT1-C1 cells demonstrated rapid proliferation, spheroid formation, invasion capability in vitro, and tumorigenesis in nude mice. Screening of antitumor agents in NCC-MRT1-C1 cells resulted in the identification of six effective drugs. In conclusion, we report the first MRT cell line from the soft tissue of an adult patient. We believe that NCC-MRT1-C1 is a useful tool for developing novel chemotherapies for MRT., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

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., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Myxofibrosarcoma (MFS) is a rare and aggressive mesenchymal malignancy characterized by complex karyotypes with heterogeneous clinical features. The standard treatment for primary MFS is curative resection; however, the utility of systemic chemotherapy and radiotherapy has not been established. Although patient-derived cancer cell lines are a key bioresource for developing novel therapies, the number of MFS cell lines available from public cell banks is limited by the rarity of the disease, and large-scale drug screening has not yet been performed. To address this issue, we aimed to establish and characterize a novel MFS cell line. We successfully established a cell line, NCC-MFS6-C1, which harbors genetic abnormalities common in MFS and exhibits aggressive phenotypes such as continuous growth, spheroid formation, and invasion in tissue culture conditions. We performed drug screening using NCC-MFS6-C1 along with five MFS cell lines established in our laboratory and clarified the response spectrum of 214 existing anticancer agents. We found that two anticancer agents, gemcitabine and romidepsin, showed considerable antiproliferative effects, and these observations were concordant with the findings of our previous report, in which these agents attenuated the proliferation of five previously reported MFS cell lines. We conclude that NCC-MFS6-C1 is a useful resource for studying MFS., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Giant cell tumor of bone (GCTB), is a rare intermediate malignant bone tumor with high local infiltrative ability, and is genetically characterized by mutation in the H3-3A gene. Standard treatment is curative surgical tumor resection. GCTB demonstrates both local recurrence and pulmonary metastasis after surgical treatment, and effective systematic chemotherapy is yet to be established. Therefore, development of novel chemotherapies for GCTB is necessary. Although patient-derived tumor cell lines are potent tools for preclinical research, 15 GCTB cell lines have been reported to date, and only four are publicly available. Thus, this study aimed to establish and characterize a novel GCTB cell line for preclinical studies on GCTB. Herein, we described the establishment of a cell line, NCC-GCTB5-C1, from the primary tumor tissue of a patient with GCTB. NCC-GCTB5-C1 was shown to harbor a mutation in the H3-3A gene, which is typical of GCTB; thus, it has useful properties for in vitro studies. We conducted the largest integrated screening analysis of 214 antitumor agents using NCC-GCTB5-C1 along with four GCTB cell lines. Romidepsin (a histone deacetylase inhibitor), camptothecin, and actinomycin D (topoisomerase inhibitors) demonstrated remarkable antitumor effects, suggesting that these antitumor agents are potential therapeutic candidates for GCTB treatment. Therefore, the NCC-GCTB5-C1 cell line could potentially contribute to the elucidation of GCTB pathogenesis and the development of novel GCTB treatments., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

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., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Dedifferentiated liposarcoma (DDLPS) is morphologically characterized by well-differentiated liposarcomas associated with high-grade non-lipogenic sarcoma and molecularly characterized by the coamplification of MDM2 and CDK4(12q14-15). DDLPS is highly aggressive, and effective systemic chemotherapy has not been developed yet. In this study, we established a novel DDLPS cell line, NCC-DDLPS6-C1, as a potential tool for the development of novel therapies. NCC-DDLPS6-C1 cells were established from surgically resected tumor tissues of a patient with DDLPS. Amplification and overexpression of MDM2 and CDK4 were observed in NCC-DDLPS6-C1 cells. NCC-DDLPS6-C1 cells proliferated rapidly, invaded aggressively, and formed spheroids. Moreover, NCC-DDLPS6-C1 cells formed tumors in mice. These observations suggested that the malignant potentials that may reflect the original features of DDLPS were retained in the NCC-DDLPS6-C1. Anticancer drugs that significantly reduced the proliferation of NCC-DDLPS6-C1 cells were identified by drug library screening. Thus, NCC-DDLPS6-C1 may recapitulate the original genotypes and phenotypes, and we conclude that the NCC-DDLPS6-C1 cell line is a useful resource for the study of DDLPS., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Myxoid liposarcoma (MLPS) is a lipogenic sarcoma, characterized by myxoid appearance histology and the presence of the FUS-DDIT3 fusion gene. MLPS shows frequent recurrence and poor prognosis after standard treatments, such as surgery. Therefore, novel therapeutic approaches for MLPS are needed. Development of novel treatments requires patient-derived cell lines to study the drug responses and their molecular backgrounds. Presently, only three cell lines of MLPS have been reported, and no line is available from public cell banks. Thus, this study aimed to establish and characterize novel MLPS cell lines. Using surgically resected tumor tissue from two patients with MLPS, two novel lines NCC-MLPS2-C1 and NCC-MLPS3-C1 were established. The presence of FUS-DDIT3 fusion, slow growth, spheroid formation, and invasive capability in these cell lines was confirmed. Growth retardation was monitored for 213 anti-cancer agents using NCC-MLPS2-C1 and NCC-MLPS3-C1 cells, and the results were integrated with the response to treatments in an MLPS cell line, NCC-MLPS1-C1, which was previously established in our laboratory. We found that romidepsin suppressed cell proliferation at considerably low concentrations in all three examined cell lines. NCC-MLPS2-C1 and NCC-MLPS3-C1 cell lines developed here represent a useful tool for basic and preclinical studies of MLPS., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Ewing sarcoma (ES) is a small round cell sarcoma that is characterized by the unique gene translocation EWSR1-FLI1. It is the second most common primary bone and soft tissue malignancy in children and adolescents. It constitutes 10-15% of all bone sarcomas and is highly aggressive and rapidly recurring. Although intensive treatments have improved the clinical outcome of ES patients, 20-25% of them exhibit metastases during diagnosis. Thus, the prognoses of these patients remain poor. Cell lines are pivotal resources to investigate the molecular background of disease progression and to develop novel therapeutic modalities. In this study, we established and characterized a novel ES cell line, NCC-ES2-C1. The presence of the EWSR1-FLI1 fusion gene in these cells was confirmed in the NCC-ES2-C1 cells. Furthermore, these cells exhibited constant proliferation, and invasion, but did not form tumors in mice. We screened the anti-tumor effects of 214 anti-cancer drugs in NCC-ES2-C1 cells and found that the drugs which effectively reduced the proliferation of NCC-ES2-C1 cells. We concluded that NCC-ES2-C1 cells are a useful resource to study functions of the EWSR1-FLI1 fusion gene, investigate phenotypic changes caused by genes and proteins, and evaluate the anti-tumor effects of novel drugs., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

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., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

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., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

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., (© 2021. Japan Human Cell Society.)

Giant cell tumor of bone (GCTB) is a rare osteolytic intermediate bone tumor that harbors a pathogenic H3F3A gene mutation and exhibits characteristic histology. The standard curative treatment for GCTB is complete surgical resection, but it frequently results in local recurrence and, more rarely, metastasis. Therefore, effective multidisciplinary treatment is needed. Although patient-derived tumor cell lines are promising tools for preclinical and basic research, there are only four available cell lines for GCTB in public cell banks. Thus, the aim of this study was to establish a novel GCTB cell line. Using surgically resected tumor tissues from a patient with GCTB, we established a cell line named NCC-GCTB4-C1. The cells harbored the typical H3F3A gene mutation and exhibited constant proliferation and invasive capabilities. After characterizing NCC-GCTB4-C1 cell behaviors, we conducted high-throughput screening of 214 anti-tumor drugs and identified seven effective drugs. Comparing the results of high-throughput screening using NCC-GCTB4-C1 cell line with the results using NCC-GCTB1-C1, NCC-GCTB2-C1, and NCC-GCTB3-C1 cell lines that we previously established, four drugs were in common effective. This study showed potential drugs for the treatment of GCTB. These data indicate that NCC-GCTB4-C1 has the potential to be a powerful tool in preclinical and basic research on GCTB., (© 2021. Japan Human Cell Society.)

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 50 values. Hence, we conclude that the NCC-MPNST6-C1 cell line is a useful resource for the study of MPNSTs., (© 2021. The Author(s) under exclusive licence to Japan Human Cell Society.)

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., (© 2021. Japan Human Cell Society.)

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., (© 2021. Japan Human Cell Society.)

Myxofibrosarcoma (MFS) is an aggressive sarcoma with a highly complex karyotype. Complete resection is the only curative treatment for MFS because it is refractory to chemotherapy. To improve clinical outcomes, it is critical to develop novel treatments for MFS. Although patient-derived cell lines play a key role in cancer research, only 12 MFS cell lines have been reported to date, and considering the diversity of the disease, more cell lines need to be established. Hence, in the present study, we established a novel MFS cell line, NCC-MFS4-C1, using a surgically resected tumor tissue from a patient with MFS. NCC-MFS4-C1 cells exhibited copy number alterations similar to those of the original tumors and showed constant proliferation, spheroid formation, and aggressive invasion. By screening a drug library, we found that actinomycin D, bortezomib, docetaxel, eribulin, and romidepsin significantly reduced the proliferation of NCC-MFS4-C1 cells. Therefore, the NCC-MFS4-C1 cell line may be a useful resource for researching MFS., (© 2021. Japan Human Cell Society.)

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., (© 2021. Japan Human Cell Society.)

Myxofibrosarcoma (MFS) is one of the most aggressive sarcomas with highly complex karyotypes and genomic profiles. Although a complete resection is required in the treatment of MFS, it is often not achieved due to its strong invasive nature. Additionally, MFS is refractory to conventional chemotherapy, leading to poor prognosis. Therefore, it is necessary to develop novel treatment modalities for MFS. Patient-derived cell lines are important tools in basic research and preclinical studies. However, only 10 MFS cell lines have been reported to date. Furthermore, among these cell lines, merely two MFS cell lines are publicly available. Hence, we established a novel MFS cell line named NCC-MFS3-C1, using a surgically resected tumor specimen from a patient with MFS. NCC-MFS3-C1 cells had copy number alterations corresponding to the original tumor. NCC-MFS3-C1 cells demonstrate constant proliferation, spheroid formation, and aggressive invasion. In drug screening tests, the proteasome inhibitor bortezomib and the histone deacetylase inhibitor romidepsin demonstrated significant antiproliferative effects on NCC-MFS3-C1 cells. Thus, the NCC-MFS3-C1 cell line is a useful tool in both basic and preclinical studies for MFS.

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.

Dedifferentiated liposarcoma (DDLPS) is a highly aggressive subtype of liposarcoma that is histologically a transition form between an atypical lipomatous tumor/well-differentiated liposarcoma and a non-lipogenic sarcoma. DDLPS is genetically characterized by a complex karyotype with copy number variations and genomic complexity. DDLPS has a poor prognosis, a high local recurrence rate, and refractory behaviors for chemotherapy and radiation, which indicate a requirement for a novel therapeutic strategy for better clinical outcomes. We report here, a novel DDLPS cell line (NCC-DDLPS2-C1) developed from a tumor tissue. NCC-DDLPS2-C1 cells showed an amplified 12q13-15 region and exhibited constant growth, spheroid formation, and invasion. High-throughput drug screening revealed distinct sensitivity between monolayer- and three-dimensional cells. Romidepsin and trabectedin especially showed high anti-proliferative effects in both culture methods of NCC-DDLPS2-C1. Thus, the NCC-DDLPS2-C1 cell line may serve as a useful resource for DDLPS studies.

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.

Pleomorphic liposarcoma (PLPS) is a rare subtype of liposarcoma, characterized by the presence of pleomorphic lipoblasts without definitive molecular aberrations; it accounts for less than 5% of all liposarcomas. PLPS is an aggressive cancer that exhibits frequent local recurrence and metastasis, with an overall 5-year survival rate of ~ 60%. Owing to the lack of effective treatment options in inoperable conditions and resistance to chemotherapeutics, novel therapies are required to treat PLPS. Although patient-derived cell lines are a critical tool for basic and pre-clinical research, only one PLPS cell line is reportedly available for analysis. A paucity of adequate cell line hinders the progress of research and treatments of PLPS. Thus, we aimed to establish and characterize a novel patient-derived cell line for PLPS. Using surgically resected tumor tissue from a 71-year-old male patient, we established the NCC-PLPS1-C1 cell line. The cells were maintained for more than 8 months and passaged ~ 40 times in the tissue culture condition. NCC-PLPS1-C1 cells were characterized by multiple genetic deletions and showed rapid growth, spheroid formation, and invasive potential. The NCC-PLPS1-C1 cells and the original tumor tissue shared similar kinase activity profiles for FES and PDGFR-β. NCC-PLPS1-C1 constantly proliferated, being suitable for the screening of anti-cancer drugs. A screen for the anti-proliferative effects of anti-cancer drugs on NCC-PLPS1-C1 cells showed a significant response for bortezomib, gemcitabine, romidepsin, topotecan, and vinblastine. In conclusion, NCC-PLPS1-C1 cells represent a useful tool for basic and pre-clinical studies related to PLPS, especially high-throughput drug screening.

Leiomyosarcoma (LMS) is a rare and aggressive mesenchymal malignancy, derived from smooth muscle cells or precursor mesenchymal stem cells for this tissue type. LMS has highly complex and unstable karyotypes, and the clinical outcomes in patients with LMS remain dismal as evidenced by the 5-year-survival of 64%. Novel therapeutic approaches are required to improve its clinical outcomes. Patient-derived cancer cell lines are indispensable as a tool to study the molecular mechanisms underlying clinical behaviors of tumor cells such as resistance to treatments, metastasis, and recurrence. However, only a limited number of LMS cell lines are publicly available, probably because of the rarity of patients with LMS, and a paucity of cell lines hinders the research on LMS. This study aimed to develop a patient-derived LMS cell line. We successfully established a cell line from the primary tumor tissue of a 90-year-old female patient with pleomorphic LMS, which we named NCC-LMS2-C1. NCC-LMS2-C1 cells were maintained as a monolayer culture for over 29 passages spanning 10 months. NCC-LMS2-C1 cells exhibited continuous growth, the ability to form spheroid, and invasion capability. We screened 213 anti-cancer drugs to find those that have anti-proliferation effects on NCC-LMS2-C1 cells, and identified a histone deacetylase inhibitor, romidepsin. In conclusion, we have established a novel LMS cell line, NCC-LMS2-C1, which will be a useful resource to study the mechanisms of LMS progression and perform high-throughput screening for anti-cancer drug discovery.

Myxofibrosarcoma (MFS) is among the most aggressive and complex sarcoma types that require novel therapeutic approaches for improved clinical outcomes. MFS displays highly complex karyotypes, and frequent alterations in p53 signaling and cell cycle checkpoint genes as well as loss-of-function mutations in NF1 and PTEN have been reported. The effects of radiotherapy and chemotherapy on MFS are limited, and complete surgical resection is the only curative treatment. Thus, the development of novel therapeutic strategies for MFS has long been long desired for MFS. Patient-derived cell lines are an essential tool for basic and translational research in oncology. However, public cell banks provide only a limited number of MFS cell lines. In this study, we aimed to develop a novel patient-derived MFS cell line, which was established from the primary tumor tissue of a 71-year-old male patient with MFS and was named NCC-MFS2-C1. A single-nucleotide polymorphism assay revealed that NCC-MFS2-C1 cells exhibited gain and loss of genetic loci. NCC-MFS2-C1 cells were maintained as a monolayer culture for over 24 passages for 10 months. The cells exhibited spindle-like morphology, continuous growth, and capacity for spheroid formation and invasion. Screening of 213 anticancer agents revealed that bortezomib, gemcitabine, romidepsin, and topotecan at low concentrations inhibited the proliferation of NCC-MFS2-C1 cells. In conclusion, we established a novel MFS cell line, NCC-MFS2-C1, which can be used for studying the molecular mechanisms underlying tumor development and for the in vitro screening of anti-cancer drugs.

Tenosynovial giant cell tumor (TGCT) is a mesenchymal tumor arising from the synovium of tendon sheath and joints, characterized by translocation t(1;2)(p13;q37). Clinical behaviors of TGCT range from favorable to locally aggressive and further research is required to lead the identification of novel therapeutic avenues for TGCT. Patient-derived cell lines are an indispensable tool for interrogating molecular mechanisms underlying the progression of disease. However, only one TGCT cell line is currently available from cell banks, and a paucity of adequate patient-derived cells hinders basic and translational research. This study aimed to establish a novel cell line of TGCT. To this end, a novel cell line, NCC-TGCT1-C1 was established from the primary tumor tissue of a 40-year-old female patient with TGCT. The cells exhibited translocation t(1;2)(p13;q37), generating COL6A3-CSF1 fusion gene. The cells were maintained as a monolayer culture through more than 30 passages over 12 months. The cells exhibited continuous growth and the ability for spheroid formation and invasion. When used in a high-throughput assay to evaluate the anti-proliferative effects of 164 anticancer drugs, the cells responded strongly to a kinase inhibitor such as gefitinib, and mitoxantrone. Our results indicate that the novel TGCT cell line, designated NCC-TGCT1-C1, was successfully established and could be used to study TGCT development and the effects of anticancer agents.

Alveolar rhabdomyosarcoma (aRMS) is a histological subtype of RMS, which is the most common pediatric and adolescent soft-tissue sarcoma, accounting for 3-4% of all pediatric malignancies. Patient-derived cells are essential tools for understanding the molecular mechanisms of poor prognosis and developing novel anti-cancer drugs. However, only a limited number of well-characterized cell lines for rhabdomyosarcoma from public cell banks is available. Therefore, we aimed to establish a novel cell line of aRMS from the tumor tissue of a patient with aRMS. The cell line was established from surgically resected tumor tissue from a 4-year-old male patient diagnosed with stage III, T2bN1M0 aRMS and was named as NCC-aRMS1-C1. The cells were maintained for more than 3 months under tissue culture conditions and passaged more than 20 times. We confirmed the presence of identical fusion gene such as PAX7-FOXO1 in both the original tumor and NCC-aRMS1-C1. The cells exhibited spheroid formation and invasion. We found that docetaxel, vincristine, ifosfamide, dacarbazine, and romidepsin showed remarkable growth-suppressive effects on the NCC-aRMS1-C1 cells. In conclusion, the NCC-aRMS1-C1 cell line exhibited characteristics that may correspond to the lymph node metastasis in aRMS and mirror its less aggressive features. Thus, it may be useful for innovative seeds for novel therapeutic strategies.

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor, accounting for approximately 5% of all primary bone tumors. GCTB is characterized by unique giant cells. It is also characterized by recurrent mutations in the histone tail of the histone variant H3.3, H3F3A, on chromosome 1, therapeutic implications of which have not been established yet. There are few effective standardized treatments for GCTB, and a novel therapy has long been required. Patient-derived cancer cells have facilitated the understanding of mechanisms underlying the etiology and progression of multiple cancers. Thus far, only 10 GCTB cell lines have been reported, and none of them are publicly available. The aim of this study was to develop an accessible patient-derived cell line of GCTB, which could be used as a screening tool for drug development. Here, we describe the establishment of a cell line, designated NCC-GCTB1-C1, from the primary tumor tissue of a male patient with GCTB on the right distal radius. NCC-GCTB1-C1 cells were maintained as a monolayer culture for over 23 passages for 7 months. These cells exhibited continuous growth, as well as spheroid formation and invasive ability. Using an oncology agent screen, we tested the effect of anticancer drugs on the proliferation of NCC-GCTB1-C1 cells. The cells displayed a remarkable response to romidepsin and vincristine. Thus, we established a novel GCTB cell line, NCC-GCTB1-C1, which could be a useful tool for studying GCTB tumorigenesis and the efficacy of anticancer drugs.

Prostate cancer cells express prostate-specific membrane antigen (PSMA). We developed an IgM type monoclonal antibody against PSMA. The antibody was coupled to poly-L-lysine and thereafter this conjugate was mixed with cationic liposomes containing plasmid DNA. The antibody-liposome complex was tested whether it could deliver the gene of interest selectively to the PSMA positive cells. As assessed by beta-galactosidase reporter gene, the transfection efficiency was 13.2% with anti-PSMA-liposome complex as compared to 4% with control IgM liposome complex. In contrast, no such differences were observed in PSMA negative PC-3, DU145 and T24 cells. Furthermore, in the suicide gene therapy in vitro with thymidine kinase gene plus ganciclovir system, anti-PSMA liposome complex demonstrated a selective growth inhibitory effect on PSMA positive LNCaP cells but not on PSMA negative cell lines.