Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells.
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.
Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224, USA.
Cheryl A
CA
Sherman-Baust
Ashani T
AT
Weeraratna
Leticia B A
LB
Rangel
Ellen S
ES
Pizer
Kathleen R
KR
Cho
Donald R
DR
Schwartz
Teresa
T
Shock
Patrice J
PJ
Morin
D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D024142:Collagen Type VI / Q000096:biosynthesis*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D010051:Ovarian Neoplasms / Q000503:physiopathology*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D024142:Collagen Type VI; D002945:Cisplatin