Establishment and characterization of NCC-DDLPS3-C1: a novel patient-derived cell line of dedifferentiated liposarcoma

• DOI: 10.1007/s13577-021-00515-1
• Publication Date: 2021-03-06T18:03:01Z
• Authors: Ryuto Tsuchiya; Yuki Yoshimatsu; Rei Noguchi; Takuya Ono; Akane Sei; Fumitaka Takeshita; Jun Sugaya; Suguru Fukushima; Akihiko Yoshida; Seiji Ohtori; Akira Kawai; Tadashi Kondo
• Keywords: 0301 basic medicine; Chromosomes, Human, Pair 12; Carcinogenesis; Gene Amplification; Cyclin-Dependent Kinase 4; Mice, Nude; Antineoplastic Agents; Proto-Oncogene Proteins c-mdm2; Liposarcoma; Middle Aged; Prognosis; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Spheroids, Cellular; Animals; Humans; Female; Neoplasm Invasiveness; Drug Screening Assays, Antitumor; Cell Proliferation

Dedifferentiated liposarcoma (DDLPS) is a highly malignant subtype of liposarcoma, with characteristic amplification of MDM2 and CDK4 (12q14-15). It is caused by the dedifferentiation of well-differentiated liposarcoma. DDLPS is refractory to conventional chemotherapy; thus, surgical resection is the primary treatment modality. However, complete resection of DDLPS is difficult because of its deep location, which results in poor prognosis. Therefore, novel systemic chemotherapy is required to improve the clinical outcome. Patient-derived cell lines are important tools in the development of novel chemotherapy. However, there are no DDLPS cell lines available from public cell banks. In this study, we established a novel DDLPS cell line, NCC-DDLPS3-C1, using a surgically resected specimen from a patient with DDLPS. NCC-DDLPS3-C1 cells retained the characteristic gene amplification of MDM2 and CDK4. In addition, other gene amplifications and losses related to the poor prognosis of DDLPS were also observed in concordance with the original tumor. The cells also exhibited rapid cell proliferation, aggressive invasion ability, spheroid formation ability, and tumorigenic ability in nude mice. Furthermore, a drug-screening test showed significant antiproliferative effects of proteasome inhibitors and HDAC inhibitors. Thus, the NCC-DDLPS3-C1 cell line should be a useful tool for the development of novel chemotherapy for DDLPS.