Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells

Cheryl A. Sherman-Baust, Ashani T. Weeraratna, Leticia B.A. Rangel, Ellen S. Pizer, Kathleen R. Cho, Donald R. Schwartz, Teresa Shock, Patrice J. Morin

Research output: Contribution to journalArticle

Abstract

The mechanisms of drug resistance in cancer are poorly understood. Serial analysis of gene expression (SAGE) profiling of cisplatin-resistant and sensitive cells revealed many differentially expressed genes. Remarkably, many ECM genes were elevated in cisplatin-resistant cells. COL6A3 was one of the most highly upregulated genes, and cultivation of cisplatin-sensitive cells in the presence of collagen VI protein promoted resistance in vitro. Staining of ovarian tumors with collagen VI antibodies confirmed collagen VI expression in vivo and suggested reorganization of the extracellular matrix in the vicinity of the tumor. Furthermore, the presence of collagen VI correlated with tumor grade, an ovarian cancer prognostic factor. These results suggest that tumor cells may directly remodel their microenvironment to increase their survival in the presence of chemotherapeutic drugs.

Original languageEnglish (US)
Pages (from-to)377-386
Number of pages10
JournalCancer cell
Volume3
Issue number4
DOIs
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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