Establishment and characterization of NCC-DDLPS1-C1: a novel patient-derived cell line of dedifferentiated liposarcoma

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CELL LINE

Establishment and characterization of NCC‑DDLPS1‑C1: a novel patient‑derived cell line of dedifferentiated liposarcoma Ryuto Tsuchiya1,2 · Yuki Yoshimatsu1 · Rei Noguchi1 · Akane Sei1 · Fumitaka Takeshita3 · Jun Sugaya4 · Suguru Fukushima4 · Akihiko Yoshida5 · Seiji Ohtori2 · Akira Kawai4 · Tadashi Kondo1  Received: 15 July 2020 / Accepted: 13 September 2020 © Japan Human Cell Society 2020

Abstract Dedifferentiated liposarcoma (DDLPS) is one of the four subtypes of liposarcomas; it is characterized by the amplification of the 12q13-15 region, which includes MDM2 and CDK4 genes. DDLPS has an extremely high local recurrence rate and is refractory to chemotherapy and radiation, which leads to poor prognosis. Therefore, a novel therapeutic strategy should be urgently established for improving the prognosis of DDLPS. Although patient-derived cell lines are important tools for basic research, there are no DDLPS cell lines available from public cell banks. Here, we report the establishment of a novel DDLPS cell line. Using the surgically resected tumor tissue from a patient with DDLPS, we established a cell line and named it NCC-DDLPS1-C1. The NCC-DDLPS1-C1 cells contained 12q13-15, 1p32, and 1q23 amplicons and highly expressed MDM2 and CDK4 proteins. NCC-DDLPS-C1 cells exhibited constant growth, spheroid formation, aggressive invasion, and tumorigenesis in mice. By screening a drug library, we identified that the proteasome inhibitor, bortezomib, had inhibitory effects on the proliferation of NCC-DDLPS1-C1 cells. We concluded that the NCC-DDLPS1-C1 cell line may serve as a useful tool for basic and pre-clinical studies of DDLPS. Keywords  Sarcoma · Dedifferentiated liposarcoma · Patient-derived cancer model · Patient-derived cell line

Introduction Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1357​7-020-00436​-5) 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



Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1‑8‑1 Inohana, Chuo‑ku, Chiba 260‑8670, Japan

3

Department of Translational Oncology, Fundamental Innovative Oncology Core Center, National Cancer Center Research Institute, 5‑1‑1 Tsukiji, Chuo‑ku, Tokyo 104‑0045, Japan

4

Department of Musculoskeletal Oncology, National Cancer Center Hospital, 5‑1‑1 Tsukiji, Chuo‑ku, Tokyo 104‑0045, Japan

5

Department of Diagnostic Pathology, National Cancer Center Hospital, 5‑1‑1 Tsukiji, Chuo‑ku, Tokyo 104‑0045, Japan







Dedifferentiated liposarcoma (DDLPS) is one of the four subtypes of liposarcoma. Each subtype of a liposarcoma (atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, and pleomorphic liposarcoma) has different clinical behaviors and genetic characteristics [1, 2]. DDLPS was first reported by Evans [3]; it is defi