Establishment of a novel patient-derived Ewing’s sarcoma cell line, NCC-ES1-C1

Oyama, Rieko; Kito, Fusako; Qiao, Zhiwei; Sakumoto, Marimu; Noguchi, Rei; Takahashi, Mami; Toki, Shunichi; Tanzawa, Yoshikazu; Yoshida, Akihiko; Kawai, Akira; Kondo, Tadashi

doi:10.1007/s11626-018-0302-2

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…In accordance to the results obtained from cell lines derived from SS, ES and ASPS in Fig. 1A , ZSTK474 induced apoptosis in PDCs established from SS (NCC-SS1-C1) [ 36 ], ES (NCC-ES1-C1) [ 37 ] but not in ASPS (NCC-ASPS1-C1) [ 38 ]. Furthermore, ZSTK474 also induced apoptosis in PDCs derived from CCS (NCC-CCS1B-C1) [ 39 ], but not in those derived from CDS (NCC-CDS2-C1) [ 40 ] and DFSP (NCC-DFSP2-C1) [ 41 ] (Fig.…”

Section: Resultssupporting

confidence: 87%

Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors

et al. 2023

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Translocation-related sarcomas (TRSs) harbor an oncogenic fusion gene generated by chromosome translocation and account for approximately one-third of all sarcomas; however, effective targeted therapies have yet to be established. We previously reported that a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, ZSTK474, was effective for the treatment of sarcomas in a phase I clinical trial. We also demonstrated the efficacy of ZSTK474 in a preclinical model, particularly in cell lines from synovial sarcoma (SS), Ewing’s sarcoma (ES) and alveolar rhabdomyosarcoma (ARMS), all of which harbor chromosomal translocations. ZSTK474 selectively induced apoptosis in all these sarcoma cell lines, although the precise mechanism underlying the induction of apoptosis remained unclear. In the present study, we aimed to determine the antitumor effect of PI3K inhibitors, particularly with regards to the induction of apoptosis, against various TRS subtypes using cell lines and patient-derived cells (PDCs). All of the cell lines derived from SS (six), ES (two) and ARMS (one) underwent apoptosis accompanied by the cleavage of poly-(ADP-ribose) polymerase (PARP) and the loss of mitochondrial membrane potential. We also observed apoptotic progression in PDCs from SS, ES and clear cell sarcoma (CCS). Transcriptional analyses revealed that PI3K inhibitors triggered the induction of PUMA and BIM and the knockdown of these genes by RNA interference efficiently suppressed apoptosis, suggesting their functional involvement in the progression of apoptosis. In contrast, TRS-derived cell lines/PDCs from alveolar soft part sarcoma (ASPS), CIC-DUX4 sarcoma and dermatofibrosarcoma protuberans failed to undergo apoptosis nor induce PUMA and BIM expression, as well as cell lines derived from non-TRSs and carcinomas. Thus, we conclude that PI3K inhibitors induce apoptosis in selective TRSs such as ES and SS via the induction of PUMA and BIM and the subsequent loss of mitochondrial membrane potential. This represents proof of concept for PI3K-targeted therapy, particularly such TRS patients.

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Section: Resultssupporting

confidence: 87%

Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors

et al. 2023

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“…The sarcoma patient‐derived models that were proteomically profiled in this study (workflow in Figure A, Table S1, Supporting Information) were previously described and represent the UPS, CCS, and plRMS subtypes. All PDXs were passaged until the third generation in mice (X1–X3) and frozen in liquid nitrogen.…”

Section: Resultsmentioning

confidence: 99%

“…The sources and generation of all PDXs and cell lines from undifferentiated pleomorphic sarcoma (UPS), clear cell sarcoma (CCS), and pleomorphic rhabdomyosarcoma (plRMS) subtypes used in this study were previously reported. Detailed descriptions of these procedures are given in the Supporting Information Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

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Species‐Specific Quantitative Proteomics Profiles of Sarcoma Patient‐Derived Models Closely Reflect Their Primary Tumors

Shiozawa¹,

Oyama²,

Takahashi³

et al. 2019

Proteomics Clinical Apps

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Purpose The purpose is to examine whether patient‐derived sarcoma models recapitulate the spectrum of sarcoma heterogeneity seen in patients. Experimental design To characterize patient‐derived models for functional studies, proteomic comparisons with originating sarcomas representative of three intrinsic subtypes by MS are performed. Results Human protein profiling is found to be retained with high fidelity in patient‐derived models. The protein profiles of patient sarcoma tumors and mouse stroma are characterized by species‐specific quantitative proteomics. Protein‐expression levels in mouse stroma are affected by the primary human tumor. The levels of stromal proteins derived from tumors are lower in PDXs and cell lines, and some human stromal proteins are replaced by the corresponding mouse proteins in PDXs. Conclusions and clinical relevance These findings suggest that the effects of the microenvironment on drug responses may not reflect those in the primary tumor. This cross‐species proteomic analysis in PDXs can potentially improve preclinical evaluation of treatment modalities and enhance the ability to predict clinical trial responses.

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“…ere are a number of studies based on patient-derived cells (PDC) and patient-derived xenograft (PDX) model in vivo. However, most of the described investigations are focused on establishment of new cell line derived from patient tumor (for example, see [63][64][65][66][67], on preclinical studies of novel or repurposed drug/combination of drugs in vitro [68][69][70][71] and in vivo [72][73][74]). Only a few studies address the optimization of STS treatment.…”

Section: Drug Sensitivity Testing On Patient-derived Sts Cellsmentioning

confidence: 99%

Current Approaches for Personalized Therapy of Soft Tissue Sarcomas

Кирсанов

Lesovaya

Fetisov

et al. 2020

Sarcoma

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Soft tissue sarcomas (STS) are a highly heterogeneous group of cancers of mesenchymal origin with diverse morphologies and clinical behaviors. While surgical resection is the standard treatment for primary STS, advanced and metastatic STS patients are not eligible for surgery. Systemic treatments, including standard chemotherapy and newer chemical agents, still play the most relevant role in the management of the disease. Discovery of specific genetic alterations in distinct STS subtypes allowed better understanding of mechanisms driving their pathogenesis and treatment optimization. This review focuses on the available targeted drugs or drug combinations based on genetic aberration involved in STS development including chromosomal translocations, oncogenic mutations, gene amplifications, and their perspectives in STS treatment. Furthermore, in this review, we discuss the possible use of chemotherapy sensitivity and resistance assays (CSRA) for the adjustment of treatment for individual patients. In summary, current trends in personalized management of advanced and metastatic STS are based on combination of both genetic testing and CSRA.

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Establishment of a novel patient-derived Ewing’s sarcoma cell line, NCC-ES1-C1

Cited by 5 publications

References 38 publications

Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors

Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors

Species‐Specific Quantitative Proteomics Profiles of Sarcoma Patient‐Derived Models Closely Reflect Their Primary Tumors

Current Approaches for Personalized Therapy of Soft Tissue Sarcomas

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