Establishment and characterization of a novel cell line, NCC-TGCT1-C1, derived from a patient with tenosynovial giant ce

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CELL LINE

Establishment and characterization of a novel cell line, NCC‑TGCT1‑C1, derived from a patient with tenosynovial giant cell tumor Rei Noguchi1 · Yuki Yoshimatsu1 · Takuya Ono1 · Akane Sei1 · Kaoru Hirabayashi2 · Iwao Ozawa3 · Kazutaka Kikuta4 · Tadashi Kondo1  Received: 6 July 2020 / Accepted: 30 August 2020 © Japan Human Cell Society 2020

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 NCCTGCT1-C1, was successfully established and could be used to study TGCT development and the effects of anticancer agents. Keywords  Tenosynovial giant cell tumor · TGCT​ · Patient-derived cell line · Anticancer drug · High-throughput screening

Introduction

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1357​7-020-00425​-8) contains supplementary material, which is available to authorized users. * Tadashi Kondo [email protected] 1



Division of Rare Cancer Research, National Cancer Center Research Institute, 5‑1‑1 Tsukiji, Chuo‑ku, Tokyo 104‑0045, Japan

2



Division of Diagnostic Pathology, Tochigi Cancer Center, 4‑9‑13 Yohnan, Utsunomiya, Tochigi 320‑0834, Japan

3

Division of Hepato‑Biliary‑Pancreatic Surgery, Tochigi Cancer Center, 4‑9‑13 Yohnan, Utsunomiya, Tochigi 320‑0834, Japan

4

Division of Musculoskeletal Oncology and Orthopaedics Surgery, Tochigi Cancer Center, 4‑9‑13 Yohnan, Utsunomiya, Tochigi 320‑0834, Japan





Tenosynovial giant cell tumor (TGCT) is a mesenchymal tumor with diverse clinical behaviors ranging from favorable to locally aggressive. The annual incidence of TGCT is estimated to be 43 cases per 1 million individuals [1]. TGCTs are derived from synovial lining cells that overexpress colony-stimulating factor-1 (CSF-1) [2], and arise in the synovium of