Abstract
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.
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References
Mastboom MJL, Verspoor FGM, Verschoor AJ, et al. Higher incidence rates than previously known in tenosynovial giant cell tumors. Acta Orthop. 2017;88:688–94.
Ravi V, Wang WL, Lewis VO. Treatment of tenosynovial giant cell tumor and pigmented villonodular synovitis. Curr Opin Oncol. 2011;23:361–6.
Savage RC, Mustafa EB. Giant cell tumor of tendon sheath (localized nodular tenosynovitis). Ann Plast Surg. 1984;13:205–10.
Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F. Soft Tissue and Bone Tumours. Geneva: WHO Press; 2020.
West RB, Rubin BP, Miller MA, et al. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A. 2006;103:690–5.
Temple HT. Pigmented villonodular synovitis therapy with MSCF-1 inhibitors. Curr Opin Oncol. 2012;24:404–8.
Möller E, Mandahl N, Mertens F, Panagopoulos I. Molecular identification of COL6A3-CSF1 fusion transcripts in tenosynovial giant cell tumors. Genes Chromosomes Cancer. 2008;47:21–5.
Reilly KE, Stern PJ, Dale JA. Recurrent giant cell tumors of the tendon sheath. J Hand Surg. 1999;24:1298–302.
Gelderblom H, Cropet C, Chevreau C, et al. Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2018;19:639–48.
Cassier PA, Gelderblom H, Stacchiotti S, et al. Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis. Cancer. 2012;118:1649–55.
Cassier PA, Italiano A, Gomez-Roca CA, et al. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 2015;16:949–56.
Tap WD, Gelderblom H, Palmerini E, et al. Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet. 2019;394:478–87.
Sharma SV, Haber DA, Settleman J. Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents. Nat Rev Cancer. 2010;10:241–53.
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.
Iorio F, Knijnenburg TA, Vis DJ, et al. A landscape of pharmacogenomic interactions in cancer. Cell. 2016;166:740–54.
Teicher BA, Polley E, Kunkel M, et al. Sarcoma cell line screen of oncology drugs and investigational agents identifies patterns associated with gene and microRNA expression. Mol Cancer Ther. 2015;14:2452–62.
Bairoch A. The cellosaurus, a cell-line knowledge resource. J Biomol Tech. 2018;29:25–38.
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.
Capes-Davis A, Reid YA, Kline MC, et al. Match criteria for human cell line authentication: where do we draw the line? Int J Cancer. 2013;132:2510–9.
Nath S, Devi GR. Three-dimensional culture systems in cancer research: focus on tumor spheroid model. Pharmacol Ther. 2016;163:94–108.
Voissiere A, Jouberton E, Maubert E, et al. Development and characterization of a human three-dimensional chondrosarcoma culture for in vitro drug testing. PLoS ONE. 2017;12:e0181340.
Herbst RS, Fukuoka M, Baselga J. Gefitinib—a novel targeted approach to treating cancer. Nat Rev Cancer. 2004;4:956–65.
Faulds D, Balfour JA, Chrisp P, Langtry HD. Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs. 1991; 41:400–49.
Acknowledgements
We appreciate the technical support of Miss Yu Kuwata (Division of Rare Cancer Research, National Cancer Center). We would like to thank the Tochigi Cancer Center Operating Room Nurse Team and the Secretary of the Medical Office for their assistance in processing and transporting the samples. We would like to thank Editage (https://www.editage.jp) for English-language editing and for their constructive comments on the manuscript.
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This research was supported by Japan Agency for Medical Research and Development (grant number 20ck0106537h0001).
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Noguchi, R., Yoshimatsu, Y., Ono, T. et al. Establishment and characterization of a novel cell line, NCC-TGCT1-C1, derived from a patient with tenosynovial giant cell tumor. Human Cell 34, 254–259 (2021). https://doi.org/10.1007/s13577-020-00425-8
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DOI: https://doi.org/10.1007/s13577-020-00425-8