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Epithelial Cancer Cell Migration

A Role for Chemokine Receptors?

Imperial Cancer Research Fund Translational Oncology Laboratory, Barts and the Royal London School of Medicine and Dentistry, London EC1M 6BQ, United Kingdom [C. J. S., J. L. W., D. M., F. R. B.], and Department of Histopathology, Division of Investigative Sciences, Imperial College School of Medicine, Hammersmith Hospital Campus, London W12 ONN, United Kingdom [G. S.]

We investigated the possibility that chemokine gradients influence migration of human ovarian epithelial tumor cells. Of 14 chemokine receptors investigated, only CXCR4 was expressed on ovarian cancer cells. CXCR4 mRNA localized to a subpopulation of tumor cells in ovarian cancer biopsies. Ovarian cancer cell lines and cells freshly isolated from ascites expressed CXCR4 protein. The CXCR4 ligand, CXCL12, was found in ascites from 63 patients. CXCL12 elicited intracellular calcium flux and directed migration and changes in integrin expression in ovarian cancer cells. CXCR4 may influence cell migration in the peritoneum, a major route for ovarian cancer spread, and could be a therapeutic target.

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