Possible angiogenic roles for claudin-4 in ovarian cancer

Abstract

Claudin proteins are frequently overexpressed in various tumors such as breast, prostate

and ovarian cancer. While their functions in cancer have not been completely elucidated,

roles in survival, adhesion, and invasion have been suggested. In order to clarify the roles

of claudins in ovarian cancer, we have performed gene expression profiling of ovarian

surface epithelial cells overexpressing claudin-4 and compared the expression patterns to

the parental, non-expressing cells. Claudin-4 expression leads to the differential expression

of several genes, including many that have previously been implicated in angiogenesis. In

particular, angiogenic cytokines, such as IL-8, were found elevated while genes of the

angiostatic interferon pathway were found down-regulated.  In vitro assays show that

claudin-4-expressing cells produce factors that can stimulate angiogenesis as measured by

tube formation and migration in HUVEC cells. In addition, an in vivo mouse dorsal

skinfold assay confirms that cells expressing claudin-4 secrete factors that can mediate

angiogenesis in the dorsal skin of mice. Our data suggest a novel function for claudin-4 in

cancer and provide an additional rationale for its common overexpression in human

tumors.