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.
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Acknowledgements
We thank Drs. M. Endo, Y. Minami, K. Shimizu, T. Mori, M. Sugawara, Y. Araki, S. Toki, and Ms. R. Nakano (Division of Musculoskeletal Oncology, National Cancer Center Hospital) for sampling tumor tissue specimens from surgically resected materials. We would like to thank Editage (http://www.editage.jp) for English language editing and constructive comments on the manuscript.
Funding
This work was supported by the National Cancer Center Research and Development Fund [26-A-3, 26-A-9, and 29-A-2].
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Supplementary material 9 (TIFF 151 kb) Supplementary Fig. 1. Presence of the fusion gene unique to synovial sarcoma in the NCC–SS1–C1 cell line was confirmed by RT-PCR
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Supplementary material 10 (TIFF 817 kb) Supplementary Fig. 2. Synovial sarcoma marker expression was analyzed in NCC–SS1–C1 cells by immunostaining
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Supplementary material 11 (TIFF 338 kb) Supplementary Fig. 3. The effect of anti-cancer drugs on NCC–SS1–C1 cell growth was assessed in screening studies. The IC50 values are summarized in Supplementary Table 8
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Supplementary material 12 (TIFF 332 kb) Supplementary Fig. 4. The growth suppressive effects of 24 tyrosine kinase inhibitors
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Kito, F., Oyama, R., Takai, Y. et al. Establishment and characterization of the NCC–SS1–C1 synovial sarcoma cell line. Human Cell 31, 167–174 (2018). https://doi.org/10.1007/s13577-018-0199-9
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DOI: https://doi.org/10.1007/s13577-018-0199-9