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

Hum Cell. 2021 Jan;34(1):260-270. doi: 10.1007/s13577-020-00436-5. Epub 2020 Sep 19.

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: Dedifferentiated liposarcoma; Patient-derived cancer model; Patient-derived cell line; Sarcoma.

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / pharmacology
  • Bortezomib / pharmacology
  • Carcinogenesis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Drug Screening Assays, Antitumor
  • Gene Expression / genetics
  • Humans
  • Liposarcoma / genetics*
  • Liposarcoma / pathology*
  • Male
  • Mice
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism

Substances

  • Antineoplastic Agents
  • Bortezomib
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4