title: 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 downregulated. 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.
authors: Laboratory of Cellular and Molecular Biology, National Institute on Aging/NIH, Baltimore, MD, USA.
authors: Jianghong
authors: J
authors: Li
authors: Srinivasulu
authors: S
authors: Chigurupati
authors: Rachana
authors: R
authors: Agarwal
authors: Mohamed R
authors: MR
authors: Mughal
authors: Mark P
authors: MP
authors: Mattson
authors: Kevin G
authors: KG
authors: Becker
authors: William H
authors: WH
authors: Wood
authors: Yongqing
authors: Y
authors: Zhang
authors: Patrice J
authors: PJ
authors: Morin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D062506:Claudin-4; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D046228:Microarray Analysis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: C568157:CLDN4 protein, human; D062506:Claudin-4; C568158:Cldn4 protein, mouse; D008565:Membrane Proteins