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Vascular Cell Adhesion Molecule-1 Is a Regulator of Ovarian Cancer Peritoneal Metastasis

Departments of ¹ Microbiology, ² Pathology, and ³ Health Evaluation Sciences and ⁴ Cancer Center, University of Virginia, Charlottesville, Virginia

Requests for reprints: Jill K. Slack-Davis, Department of Microbiology, University of Virginia, P. O. Box 800734, Charlottesville, VA 22908. Phone: 434-924-5341; Fax: 434-982-0689; E-mail: jks6a{at}virginia.edu.

Key Words: VCAM-1 • integrin • ovarian cancer • metastasis • migration

Ovarian cancers metastasize by attaching to and invading through the mesothelium, a single layer of mesothelial cells lining the peritoneal cavity. The presence of invasive peritoneal metastases is associated with a poor prognosis for ovarian cancer (5-year survival <25%). Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface receptor that mediates leukocyte attachment and extravasation across endothelial and mesothelial monolayers at sites of inflammation. Membranous VCAM-1 expression was observed on the mesothelium of 13 of 14 women with ovarian cancer compared with 6 of 15 who were cancer-free. Using a cell culture model system of mesothelial invasion, highly tumorigenic SKOV-3 and ES-2 cells were 2.5 to 3 times more efficient in transmigration through the mesothelial monolayer compared with poorly tumorigenic OVCAR-3 cells. Blocking antibodies to, or small interfering RNA knockdown of, VCAM-1 or its ligand ₄β₁ integrin significantly decreased, but did not completely inhibit, transmigration of SKOV-3 cells through mesothelial monolayers. Furthermore, using a mouse model of ovarian cancer metastasis, treatment with VCAM-1 function-blocking antibodies decreased tumor burden and increased survival. Together, these observations implicate VCAM-1-₄β₁ integrin interactions in the regulation of ovarian cancer cell mesothelial invasion and metastatic progression and offer the possibility of novel therapeutic targets. [Cancer Res 2009;69(4):1469–76]

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				Correction: Article on VCAM-1 and Ovarian Cancer Metastasis Cancer Res., March 15, 2009; 69(6): 2694 - 2694. [Full Text] [PDF]