Possible angiogenic roles for claudin-4 in ovarian cancer

    Authors

    J. H. Li; S. Chigurupati; R. Agarwal; M. R. Mughal; M. P. Mattson; K. G. Becker; W. H. Wood; Y. Q. Zhang;P. J. Morin

    Abbreviated Journal Title

    Cancer Biol. Ther.

    Keywords

    ovarian cancer; expression profiling; claudin; interleukin; interferon; angiogenesis; SURFACE EPITHELIAL-CELLS; DIFFERENTIAL GENE-EXPRESSION; ENDOTHELIAL; GROWTH-FACTOR; TIGHT JUNCTION PROTEINS; HUMAN-MELANOMA; MATRIX; METALLOPROTEINASES; INHIBIT ANGIOGENESIS; REDUCED EXPRESSION; SEROUS; PAPILLARY; TUMOR-GROWTH; Oncology

    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.

    Journal Title

    Cancer Biology & Therapy

    Volume

    8

    Issue/Number

    19

    Publication Date

    1-1-2009

    Document Type

    Article

    Language

    English

    First Page

    1806

    Last Page

    1814

    WOS Identifier

    WOS:000272795200013

    ISSN

    1538-4047

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