CD44 and β1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins

R. C. Casey, Amy P Skubitz

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Epithelial cancer of the ovary spreads by implantation of tumor cells onto the mesothelial cells that line the peritoneal cavity. The aim of this study was to identify the cell-matrix interactions that mediate ovarian carcinoma cell migration toward components of the mesothelial cell-associated extracellular matrix. The human ovarian carcinoma cell lines NIH:OVCAR5 and SKOV3 were analyzed by flow cytometry for the expression of cell surface receptors. The ability of those receptors to mediate ovarian carcinoma cell migration toward fibronectin, type IV collagen, and laminin was determined. A monoclonal antibody against the β1 integrin subunit abrogated the migration of both cell lines toward the extracellular matrix proteins. Blocking antibodies against alpha integrin subunits suggest that ovarian carcinoma cell migration toward fibronectin is primarily mediated by the α5β1 integrin, type IV collagen by the α2β1 integrin, and laminin by the α6β1 integrin. These results suggest that ovarian carcinoma cell migration is regulated by multiple β1 integrin-matrix interactions. Significant reduction of cell migration was observed with a monoclonal antibody against CD44 that blocks the hyaluronan-binding site of CD44, but not with an antibody that binds at an alternate site on CD44. Intact hyaluronan and/or hyaluronan oligomers also inhibited cell migration, suggesting that the CD44-hyaluronan interaction provides an integrin-independent mechanism of control for ovarian carcinoma cell migration. These results suggest that ovarian carcinoma cell migration is regulated by both integrin-dependent mechanisms, involving the interaction of β1 integrins with extracellular matrix proteins, and an integrin-independent mechanism that involves the interaction of CD44 and hyaluronan.

Original languageEnglish (US)
Pages (from-to)67-75
Number of pages9
JournalClinical and Experimental Metastasis
Volume18
Issue number1
DOIs
StatePublished - Dec 1 2000

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Extracellular Matrix Proteins
Integrins
Cell Movement
Carcinoma
Hyaluronic Acid
Collagen Type IV
Laminin
Fibronectins
Cell Line
Monoclonal Antibodies
Integrin alpha Chains
Blocking Antibodies
Peritoneal Cavity
Cell Surface Receptors
Cellular Structures
Cell Communication
Ovarian Neoplasms
Extracellular Matrix
Flow Cytometry
Binding Sites

Keywords

  • CD44
  • Cell migration
  • Extracellular matrix
  • Hyaluronan
  • Integrin
  • Ovarian carcinoma

Cite this

CD44 and β1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins. / Casey, R. C.; Skubitz, Amy P.

In: Clinical and Experimental Metastasis, Vol. 18, No. 1, 01.12.2000, p. 67-75.

Research output: Contribution to journalArticle

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