Possible angiogenic roles for claudin-4 in ovarian cancer

Jianghong Li, Srinivasulu Chigurupati, Rachana Agarwal, Mohamed R. Mughal, Mark P. Mattson, Kevin G. Becker, William H. Wood, Yongqing Zhang, Patrice J. Morin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1806-1814
Number of pages9
JournalCancer Biology and Therapy
Volume8
Issue number19
DOIs
StatePublished - Oct 10 2009

Keywords

  • Angiogenesis
  • Claudin
  • Expression profiling
  • Interferon
  • Interleukin
  • Ovarian cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

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