Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma

Tumour Biol. 2016 Feb;37(2):2341-51. doi: 10.1007/s13277-015-4050-6. Epub 2015 Sep 15.

Abstract

Approximately 50-70 % of patients with retroperitoneal or intraabdominal sarcoma develop a relapse after surgical therapy, including peritoneal sarcomatosis, an extremely rare site of metastatic disease which is associated with an extremely poor prognosis. Accordingly, the establishment of a permanent cell line derived from peritoneal sarcomatosis might provide a helpful tool to understand the biological behavior and to develop new therapeutic strategies. Thus, we established and characterized a liposarcoma cell line (Lipo-DUE1) from a peritoneal sarcomatosis that was permanently cultured without showing any morphological changes. Lipo-DUE1 cells exhibited a spindle-shaped morphology and positive staining for S100. Tumorigenicity was demonstrated in vitro by invasion and migration assays and in vivo by using a subcutaneous xenograft mouse model. In addition, aCGH analysis revealed concordant copy number variations on chromosome 12q in the primary tumor, peritoneal sarcomatosis, and Lipo-DUE1 cells that are commonly observed in liposarcoma. Chemotherapeutic sensitivity assays revealed a pronounced drug-resistant phenotype of Lipo-DUE1 cells to conventionally used chemotherapeutic agents. In conclusion, we describe for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies.

Keywords: Cell culture model; DDLPS; Liposarcoma; Peritoneal sarcomatosis; WDLPS.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology*
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line, Tumor / pathology*
  • Cell Movement / genetics
  • Cell Movement / physiology
  • DNA Copy Number Variations / genetics
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology
  • Female
  • Humans
  • Liposarcoma / genetics
  • Liposarcoma / pathology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Peritoneum / pathology*