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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
IARC. WHO classification of tumours of soft tissue and bone. 5th ed. Lyon: IARC; 2020.
Stacchiotti S, Van Tine BA. Synovial sarcoma: current concepts and future perspectives. J Clin Oncol. 2018;36:180–7.
Ferrari A, Gronchi A, Casanova M, et al. Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer. 2004;101:627–34.
Palmerini E, Staals EL, Alberghini M, et al. Synovial sarcoma: retrospective analysis of 250 patients treated at a single institution. Cancer. 2009;115:2988–98.
dos Santos NR, de Bruijn DRH, van Kessel AG. Molecular mechanisms underlying human synovial sarcoma development. Genes Chromosomes Cancer. 2001;30:1–14.
Jones KB, Barrott JJ, Xie M, et al. The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis. Oncogene. 2016;35:5021–32.
Szymanska J, Serra M, Skytting B, et al. Genetic imbalances in 67 synovial sarcomas evaluated by comparative genomic hybridization. Genes Chromosomes Cancer. 1998;23:213–9.
Skytting BT, Szymanska J, Aalto Y, et al. Clinical importance of genomic imbalances in synovial sarcoma evaluated by comparative genomic hybridization. Cancer Genet Cytogenet. 1999;115:39–46.
Nakagawa Y, Numoto K, Yoshida A, et al. Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization. J Cancer Res Clin Oncol. 2006;132:444–50.
Lagarde P, Przybyl J, Brulard C, et al. Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas. J Clin Oncol. 2013;31:608–15.
Orbach D, Mosseri V, Pissaloux D, et al. Genomic complexity in pediatric synovial sarcomas (Synobio study): the European pediatric soft tissue sarcoma group (EpSSG) experience. Cancer Med. 2018;7:1384–93.
Sultan I, Rodriguez-Galindo C, Saab R, Yasir S, Casanova M, Ferrari A. Comparing children and adults with synovial sarcoma in the surveillance, epidemiology, and end results program, 1983 to 2005: an analysis of 1268 patients. Cancer. 2009;115:3537–47.
Vlenterie M, Litiere S, Rizzo E, et al. Outcome of chemotherapy in advanced synovial sarcoma patients: review of 15 clinical trials from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group; setting a new landmark for studies in this entity. Eur J Cancer. 2016;58:62–72.
Lai JP, Rosenberg AZ, Miettinen MM, Lee CC. NY-ESO-1 expression in sarcomas: a diagnostic marker and immunotherapy target. Oncoimmunology. 2012;1:1409–10.
Somaiah N, Chawla SP, Block MS, et al. A phase 1b study evaluating the safety, tolerability, and immunogenicity of CMB305, a lentiviral-based prime-boost vaccine regimen, in patients with locally advanced, relapsed, or metastatic cancer expressing NY-ESO-1. Oncoimmunology. 2020;9:1847846.
Pollack SM. The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients. Expert Rev Vaccines. 2018;17:107–14.
Ben-David U, Beroukhim R, Golub TR. Genomic evolution of cancer models: perils and opportunities. Nat Rev Cancer. 2019;19:97–109.
Saito S, Morita K, Kohara A, et al. Use of BAC array CGH for evaluation of chromosomal stability of clinically used human mesenchymal stem cells and of cancer cell lines. Hum Cell. 2011;24:2–8.
Ben-David U, Siranosian B, Ha G, et al. Genetic and transcriptional evolution alters cancer cell line drug response. Nature. 2018;560:325–30.
Yang W, Soares J, Greninger P, et al. Genomics of drug sensitivity in cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41:D955–61.
Barretina J, Caponigro G, Stransky N, et al. The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483:603–7.
Goodspeed A, Heiser LM, Gray JW, Costello JC. Tumor-derived cell lines as molecular models of cancer pharmacogenomics. Mol Cancer Res. 2016;14:3–13.
Hattori E, Oyama R, Kondo T. Systematic review of the current status of human sarcoma cell lines. Cells. 2019;8:157.
Bairoch A. The cellosaurus, a cell-line knowledge resource. J Biomol Tech. 2018;29:25–38.
Kito F, Oyama R, Takai Y, et al. Establishment and characterization of the NCC-SS1-C1 synovial sarcoma cell line. Hum Cell. 2018;31:167–74.
Oyama R, Kito F, Sakumoto M, et al. Establishment and proteomic characterization of a novel synovial sarcoma cell line, NCC-SS2-C1. In Vitro Cell Dev Biol Anim. 2018;54:392–9.
Yoshimatsu Y, Noguchi R, Tsuchiya R, et al. Establishment and characterization of NCC-SS3-C1: a novel patient-derived cell line of synovial sarcoma. Hum Cell. 2020;33:877–85.
Yoshimatsu Y, Noguchi R, Tsuchiya R, et al. Establishment and characterization of NCC-CDS2-C1: a novel patient-derived cell line of CIC-DUX4 sarcoma. Hum Cell. 2020;33:427–36.
Sin Y, Yoshimatsu Y, Noguchi R, et al. Establishment and characterization of a novel alveolar rhabdomyosarcoma cell line, NCC-aRMS1-C1. Hum Cell. 2020;33:1311–20.
Billiau A, Edy VG, Heremans H, et al. Human interferon: mass production in a newly established cell line, MG-63. Antimicrob Agents Chemother. 1977;12:11–5.
von Mehren M, Joensuu H. Gastrointestinal stromal tumors. J Clin Oncol. 2018;36:136–43.
Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370:1189–97.
Roberts PJ. Clinical use of crizotinib for the treatment of non-small cell lung cancer. Biologics. 2013;7:91–101.
Fleuren EDG, Vlenterie M, van der Graaf WTA, et al. Phosphoproteomic profiling reveals ALK and MET as novel actionable targets across synovial sarcoma subtypes. Cancer Res. 2017;77:4279–92.
Laporte AN, Barrott JJ, Yao RJ, et al. HDAC and proteasome inhibitors synergize to activate pro-apoptotic factors in synovial sarcoma. PLoS ONE. 2017;12:e0169407.
We thank Drs. F Nakatani, E Kobayashi, S Fukushima, M Nakagawa, T Komatsubara, M Saito, C Sato (Department of Musculoskeletal Oncology), Drs. T Shibayama, and H Tanaka (Department of Diagnostic Pathology), National Cancer Center Hospital, for sampling tumor tissue specimens from surgically resected materials. We also appreciate the technical assistance provided by Ms. Y Kuwata (Division of Rare Cancer Research). We appreciate the technical support provided by Ms. Y Shiotani, Mr. N Uchiya, and Dr. T Imai (Central Animal Division, National Cancer Center Research Institute). We would also like to thank Editage (www.editage.jp) for their help with English language editing and their constructive comments on the manuscript. This research was technically assisted by the Fundamental Innovative Oncology Core at the National Cancer Center.
This research was supported by the Japan Agency for Medical Research and Development (Grant Number 20ck0106537h0001).
Conflict of interest
The authors declare that they have no conflict of interest.
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the ethics committee of the National Cancer Center (Approval Number 2004-050).
Written informed consent for publication was provided by the patient.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Below is the link to the electronic supplementary material.
About this article
Cite this article
Tsuchiya, R., Yoshimatsu, Y., Noguchi, R. et al. Establishment and characterization of NCC-SS4-C1: a novel patient-derived cell line of synovial sarcoma. Human Cell (2021). https://doi.org/10.1007/s13577-021-00509-z
- Synovial sarcoma
- Patient-derived cancer model
- Patient-derived cell line
- Drug screening