Establishment and characterization of the NCC–SS1–C1 synovial sarcoma cell line

Abstract

Synovial sarcoma is an aggressive mesenchymal malignancy characterized by unique gene fusions. Tissue culture cells are essential tools for further understanding tumorigenesis and anti-cancer drug development; however, only a limited number of well-characterized synovial sarcoma cell lines exist. Thus, the objective of this study was to establish a patient-derived synovial sarcoma cell line. We established a synovial sarcoma cell line from tumor tissue isolated from a 72-year-old female patient. Prepared cells were analyzed for the presence of gene fusions by fluorescence in situ hybridization, RT-PCR, and karyotyping. In addition, the resulting cell line was characterized by viability, short tandem repeat, colony and spheroid formation, and invasion analyses. Differences in gene enrichment between the primary tumor and cell line were examined by mass spectrometric protein expression profiling and KEGG pathway analysis. Our analyses revealed that the primary tumor and NCC-SS1-C1 cell line harbored the SS18-SSX1 fusion gene typical of synovial sarcoma and similar proteomics profiles. In vitro analyses also confirmed that the established cell line harbored invasive, colony-forming, and spheroid-forming potentials. Moreover, drug screening with chemotherapeutic agents and tyrosine kinase inhibitors revealed that doxorubicin, a subset of tyrosine kinase inhibitors, and several molecular targeting drugs markedly decreased NCC-SS1-C1 cell viability. Results from the present study support that the NCC-SS1-C1 cell line will be an effective tool for sarcoma research.

Exploration of Potential Ewing Sarcoma Drugs from FDA-Approved Pharmaceuticals through Computational Drug Repositioning, Pharmacogenomics, Molecular Docking, and MD Simulation Studies

“…Prior data showed that SLC12A3 is involved in different diseases such as sarcoma, neoplasms, chondrosarcoma, and adult synovial sarcoma, respectively. 42 Similarly, KCNE1, KCNQ1, and APEX1 are linked with atrial fibrillation, 81 adenocarcinomas, 82 and adenocarcinoma of the lung. 83 …”

“…Literature reports also showed that ABCB1 has a good correlation with some diseases such as osteosarcoma of bone, childhood osteosarcoma, sarcoma of soft tissues, fibrosarcoma, adult fibrosarcoma, and peripheral primitive neuroectodermal tumor. − Another report showed that the KCNH1 and HPSE genes are linked with multiple bone-associated diseases such as childhood osteosarcoma, fibrosarcoma, and synovial sarcoma. − Indapamide interacts with SLC12A3, KCNE1, KCNQ1, and APEX1 with different scoring values. Prior data showed that SLC12A3 is involved in different diseases such as sarcoma, neoplasms, chondrosarcoma, and adult synovial sarcoma, respectively . Similarly, KCNE1, KCNQ1, and APEX1 are linked with atrial fibrillation, adenocarcinomas, and adenocarcinoma of the lung …”

“…Prior data showed that SLC12A3 is involved in different diseases such as sarcoma, neoplasms, chondrosarcoma, and adult synovial sarcoma, respectively. 42 Similarly, KCNE1, KCNQ1, and APEX1 are linked with atrial fibrillation, 81 adenocarcinomas, 82 and adenocarcinoma of the lung. 83 Another screened drug, delavirdine, showed possible interactions with different genes such as ABCG2, ABCC3, ABCC2, ABCC1, and ABCB1 with good interaction scoring values.…”

Current Approaches for Personalized Therapy of Soft Tissue Sarcomas

“…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.…”

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

“…It remains however unclear how well these preclinical tumor models recapitulate patient tumor biology. We therefore developed sarcoma patient‐derived models for proteomic and functional studies, and tried to assess whether PDXsretain their proteomic characteristics with successive passaging …”