RESUMEN
Desmoplastic malignant pleural mesothelioma (DMM) is a rare histological variant of malignant pleural mesothelioma, which is a highly aggressive neoplasm of the mesothelium. DMM is associated with distant metastases and short survival. Effective treatments for DMM are not established and the development of histotype-tailored treatments is difficult due to the rarity of the disease. Although patient-derived cancer models are crucial tools for the development of novel therapeutics, they are difficult to obtain for DMM; no DMM cell lines or xenografts are available from public biobanks and only two cell lines have been reported. Thus, the present study aimed to establish a novel cell line of DMM as a resource for drug screening. A cell line of DMM was established, designated as NCC-DMM1-C1, using surgically resected tumor tissues from a 73-year-old male patient with DMM. Characteristics of NCC-DMM1-C1 cells were examined, such as growth, spheroid formation and invasion capability. Drug targets and anti-cancer drugs with anti-proliferative efficacy were examined using a comprehensive kinase activity assay and drug screening of 213 anti-cancer agents, respectively. NCC-DMM1-C1 exhibited fast growth, spheroid formation and invasion capability, suggesting that the NCC-DMM1-C1 cells retained the aggressive features of DMM. NCC-DMM1-C1 cells and the tumor tissue shared common activity profiles of kinases, which included FES, Wee1, platelet-derived growth factor receptor-ß and Src. The drug screening revealed that bortezomib, fostamatinib, gemcitabine, homoharringtonine and vinorelbine had anti-proliferative effects, which have not been previously reported for DMM. It was concluded that NCC-DMM1-C1 cells may be a useful tool for the study of DMM.
RESUMEN
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.
Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Técnicas de Cultivo de Célula/métodos , Fibrosarcoma/genética , Fibrosarcoma/patología , Proteína FUS de Unión a ARN/genética , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Línea Celular Tumoral , Variaciones en el Número de Copia de ADN , Ensayos de Selección de Medicamentos Antitumorales/métodos , Femenino , Fusión Génica , Humanos , Persona de Mediana Edad , Clasificación del TumorRESUMEN
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.
Asunto(s)
Neoplasias de Cabeza y Cuello , Rabdomiosarcoma , Sarcoma , Adulto , Antineoplásicos/farmacología , Bortezomib/farmacología , Línea Celular Tumoral , Dactinomicina/farmacología , Depsipéptidos/farmacología , Fusión Génica , Neoplasias de Cabeza y Cuello/clasificación , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Proteínas Musculares/genética , Mutación , Proteína MioD/genética , Coactivador 2 del Receptor Nuclear/genética , Rabdomiosarcoma/clasificación , Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Sarcoma/clasificación , Sarcoma/genética , Sarcoma/patología , Trabectedina/farmacología , Factores de Transcripción/genéticaRESUMEN
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.
Asunto(s)
Fibroma/patología , Sarcoma/patología , Anciano , Bortezomib/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Depsipéptidos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Fibroma/genética , Humanos , Invasividad Neoplásica , Sarcoma/genética , Esferoides Celulares/patologíaRESUMEN
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.
Asunto(s)
Carcinogénesis/genética , Carcinogénesis/patología , Liposarcoma/genética , Liposarcoma/patología , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/genética , Cromosomas Humanos Par 12/genética , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Amplificación de Genes , Humanos , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica/genética , Pronóstico , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Esferoides Celulares/patologíaRESUMEN
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.
Asunto(s)
Liposarcoma/genética , Liposarcoma/patología , Anciano de 80 o más Años , Antineoplásicos/farmacología , Técnicas de Cultivo de Célula/métodos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cromosomas Humanos Par 12/genética , Depsipéptidos/farmacología , Femenino , Dosificación de Gen , Humanos , Cariotipo , Invasividad Neoplásica , Esferoides Celulares/patología , Trabectedina/farmacologíaRESUMEN
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.
Asunto(s)
Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Sarcoma Sinovial/genética , Sarcoma Sinovial/patología , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Fusión Génica , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Esferoides Celulares/patología , MusloRESUMEN
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.
Asunto(s)
Tumor de Células Gigantes de las Vainas Tendinosas/genética , Tumor de Células Gigantes de las Vainas Tendinosas/patología , Adulto , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Colágeno Tipo VI/genética , Femenino , Gefitinib/farmacología , Fusión Génica/genética , Humanos , Factor Estimulante de Colonias de Macrófagos/genética , Mitoxantrona/farmacología , Invasividad Neoplásica , Translocación Genética/genéticaRESUMEN
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.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Fibroma/genética , Fibroma/patología , Anciano , Antineoplásicos/farmacología , Bortezomib/farmacología , Línea Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Depsipéptidos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Reducción Gradual de Medicamentos , Fibroma/terapia , Humanos , Mutación con Pérdida de Función , Masculino , Invasividad Neoplásica , Neurofibromina 1/genética , Fosfohidrolasa PTEN/genética , Topotecan/farmacología , GemcitabinaRESUMEN
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-ß. 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.
Asunto(s)
Liposarcoma/genética , Liposarcoma/patología , Antineoplásicos/farmacología , Bortezomib/farmacología , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Depsipéptidos/farmacología , Ensayos de Selección de Medicamentos Antitumorales/métodos , Eliminación de Gen , Genes Relacionados con las Neoplasias , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , GemcitabinaRESUMEN
Myxoid liposarcoma is a rare mesenchymal malignancy, which is characterized by a FUS-DDIT3 fusion known as chromosomal translocation t(12;16)(q13;p11) and arises in the fat tissue. Although surgery with radiation has been established as a standard treatment, myxoid liposarcoma shows frequent recurrence and poor prognosis, thus requiring new therapeutic approaches. Patient-derived cell lines represent a critical tool for basic and preclinical research. However, only two such myxoid liposarcoma cell lines have been reported, and they are not available in cell banks. The aim of this study was to establish and characterize a novel myxoid liposarcoma cell line. Using surgically resected tumor tissue from a 47-year-old male patient, we established the NCC-MLPS1-C1 cell line. NCC-MLPS1-C1 cells were characterized by FUS-DDIT3 fusion, slow growth, spheroid formation, and invasive capability. We screened the effect of anti-cancer agents on the proliferation of NCC-MLPS1-C1 cells. The cells displayed a remarkable response to multitarget kinase inhibitors of RET, PDGFR-ß, VEGFR, or FGFR. NCC-MLPS1-C1 cells and the tumor tissue shared common profiles of kinase activity including identified drug targets, such as RET and PDGFR-ß. We believe that NCC-MLPS1-C1 cells will represent a useful tool for basic and preclinical studies of myxoid liposarcoma.
Asunto(s)
Liposarcoma Mixoide/genética , Liposarcoma Mixoide/patología , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Fusión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-ret , Proteína FUS de Unión a ARN/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Factor de Transcripción CHOP/genéticaRESUMEN
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.
Asunto(s)
Leiomiosarcoma/patología , Anciano de 80 o más Años , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Depsipéptidos/farmacología , Descubrimiento de Drogas , Ensayos de Selección de Medicamentos Antitumorales/métodos , Femenino , Humanos , Leiomiosarcoma/tratamiento farmacológico , Invasividad NeoplásicaRESUMEN
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.
Asunto(s)
Liposarcoma/genética , Liposarcoma/patología , Anciano , Animales , Antineoplásicos/farmacología , Bortezomib/farmacología , Carcinogénesis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Expresión Génica/genética , Humanos , Masculino , Ratones , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismoRESUMEN
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.
Asunto(s)
Neoplasias Óseas , Técnicas de Cultivo de Célula/métodos , Tumor Óseo de Células Gigantes , Antineoplásicos/farmacología , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica , Desarrollo de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Tumor Óseo de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , Invasividad NeoplásicaRESUMEN
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.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Sarcoma de Parte Blanda Alveolar , Antineoplásicos/farmacología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Línea Celular Tumoral , Descubrimiento de Drogas , Ensayos de Selección de Medicamentos Antitumorales , Fusión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Oncología Médica , Persona de Mediana Edad , Sarcoma de Parte Blanda Alveolar/genética , Sarcoma de Parte Blanda Alveolar/patologíaRESUMEN
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.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Rabdomiosarcoma Alveolar , Sarcoma de Parte Blanda Alveolar , Antineoplásicos/farmacología , Línea Celular Tumoral , Preescolar , Desarrollo de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Proteína Forkhead Box O1/genética , Fusión Génica , Humanos , Metástasis Linfática , Masculino , Estadificación de Neoplasias , Factor de Transcripción PAX7/genética , Rabdomiosarcoma Alveolar/genética , Rabdomiosarcoma Alveolar/patología , Sarcoma de Parte Blanda Alveolar/genética , Sarcoma de Parte Blanda Alveolar/patologíaRESUMEN
Dermatofibrosarcoma protuberans (DFSP) is the most common dermal sarcoma; it is characterized by the presence of the COL1A1-PDGFB translocation, which causes the constitutive activation of the platelet-derived growth factor ß (PDGFB) signaling pathway. DFSP frequently exhibits local recurrence and is refractory to conventional chemotherapy. Therefore, a novel therapeutic strategy is required for improving the prognosis of DFSP. Although patient-derived cell lines are important tools for pre-clinical studies, currently, only a few such cell lines are available for DFSP in cell banks. Here, we report the establishment of a novel DFSP cell line. Using a surgically resected metastatic tumor tissue from a patient with DFSP, we established a cell line called NCC-DFSP3-C1. The NCC-DFSP3-C1 cells had a COL1A1-PDGFB translocation and retained the same copy number aberrations as the original tumor tissue. NCC-DFSP3-C1 cells exhibited constant growth, spheroid formation, and invasive ability. By screening a drug library, we identified anti-cancer agents with inhibitory effects on the proliferation of NCC-DFSP3-C1 cells; these anti-cancer agents included proteasomal, histone deacetylase, and kinase inhibitors. We concluded that the NCC-DFSP3-C1 cell line may serve as a useful tool for performing basic and pre-clinical studies on DFSP.
Asunto(s)
Dermatofibrosarcoma/genética , Dermatofibrosarcoma/patología , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/genética , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Histona Desacetilasas/farmacología , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-sis/genética , Proteínas Proto-Oncogénicas c-sis/metabolismo , Transducción de Señal/genética , Transducción de Señal/fisiología , Translocación GenéticaRESUMEN
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.
Asunto(s)
Sarcoma Sinovial/genética , Sarcoma Sinovial/patología , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Fusión Génica , Humanos , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genéticaRESUMEN
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.
Asunto(s)
Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Antineoplásicos/farmacología , Línea Celular Tumoral , Dactinomicina/farmacología , Humanos , Proteína MioD/genética , Mutación PuntualRESUMEN
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.