Establishment and characterization of NCC-MFS2-C1 : a novel patient-derived cancer cell line of myxofibrosarcoma

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CELL LINE

Establishment and characterization of NCC‑MFS2‑C1: a novel patient‑derived cancer cell line of myxofibrosarcoma Rei Noguchi1 · Yuki Yoshimatsu1 · Takuya Ono1 · Akane Sei1 · Kaoru Hirabayashi2 · Iwao Ozawa3 · Kazutaka Kikuta4 · Tadashi Kondo1,2  Received: 20 July 2020 / Accepted: 22 August 2020 © Japan Human Cell Society 2020

Abstract Myxofibrosarcoma (MFS) is among the most aggressive and complex sarcoma types that require novel therapeutic approaches for improved clinical outcomes. MFS displays highly complex karyotypes, and frequent alterations in p53 signaling and cell cycle checkpoint genes as well as loss-of-function mutations in NF1 and PTEN have been reported. The effects of radiotherapy and chemotherapy on MFS are limited, and complete surgical resection is the only curative treatment. Thus, the development of novel therapeutic strategies for MFS has long been long desired for MFS. Patient-derived cell lines are an essential tool for basic and translational research in oncology. However, public cell banks provide only a limited number of MFS cell lines. In this study, we aimed to develop a novel patient-derived MFS cell line, which was established from the primary tumor tissue of a 71-year-old male patient with MFS and was named NCC-MFS2-C1. A single-nucleotide polymorphism assay revealed that NCC-MFS2-C1 cells exhibited gain and loss of genetic loci. NCC-MFS2-C1 cells were maintained as a monolayer culture for over 24 passages for 10 months. The cells exhibited spindle-like morphology, continuous growth, and capacity for spheroid formation and invasion. Screening of 213 anticancer agents revealed that bortezomib, gemcitabine, romidepsin, and topotecan at low concentrations inhibited the proliferation of NCC-MFS2-C1 cells. In conclusion, we established a novel MFS cell line, NCC-MFS2-C1, which can be used for studying the molecular mechanisms underlying tumor development and for the in vitro screening of anti-cancer drugs. Keywords  Myxofibrosarcoma · Rare cancer · Patient-derived cell line · Drug screening

Introduction

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1357​7-020-00420​-z) 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





Myxofibrosarcoma (MFS) is one of the most aggressive soft tissue sarcomas, accounting for approximately 5% of soft tissue sarcoma diagnoses. MFS commonly occurs in the elderly population, particularly in the limbs [1]. It displays highly complex kary