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Experimental Biology and Medicine 231:1646-1652 (2006)
© 2006 Society for Experimental Biology and Medicine


ORIGINAL RESEARCH ARTICLE

Paracrine VEGF/VE-Cadherin Action on Ovarian Cancer Permeability

Limin Hu*, Napoleone Ferrara{dagger} and Robert B. Jaffe*,1

* Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143-0556; {dagger} Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080

To whom requests for reprints should be addressed at 1 Center for Reproductive Sciences, University of California, San Francisco, 505 Parnassus Avenue, HSW 1450, San Francisco, CA 94143-0556. E-mail: jaffer{at}obgyn.ucsf.edu

Ascites formation associated with neoplasms is most likely due to increased vascular permeability, a process in which vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) plays a pivotal role. We hypothesized that tumor-derived VEGF/VPF modulates ascites formation through a paracrine effect on both tumor and peritoneal vessels. We investigated human vascular endothelial permeability using a newly developed dual-chamber permeability assay by co-culturing human umbilical vein cells with and without ovarian cancer cell lines (OVCAR-3, Hey-A8, and OCC-1) in the presence or absence of a human VEGF monoclonal antibody and VE-cadherin function–blocking antibody. This method permits determination of mechanisms by which substances released from neoplasms and other sources of vascular endothelial cell secretagogues modulate vascular permeability and likely other pathologic states.

Key Words: vascular permeability • ovarian cancer • VEGF • VE-cadherin







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