Secreted Frizzled-Related Protein 4. An Angiogenesis Inhibitor

A. Muley, S. Majumder, G.K. Kolluru, Stephen Parkinson, Helena Viola, Livia Hool, Frank Arfuso, Ruth Ganss, Arunasalam Dharmarajan, S. Chatterjee

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

Wnt signaling is involved in developmental processes, cell proliferation, and cell migration. Secreted frizzled-related protein 4 (sFRP4) has been demonstrated to be a Wnt antagonist; however, its effects on endothelial cell migration and angiogenesis have not yet been reported. Using various in vitro assays, we show that sFRP4 inhibits endothelial cell migration and the development of sprouts and pseudopodia as well as disrupts the stability of endothelial rings in addition to inhibiting proliferation. sFRP4 interfered with endothelial cell functions by antagonizing the canonical Wnt/beta-catenin signaling pathway and the Wnt/planar cell polarity pathway. Furthermore, sFRP4 blocked the effect of vascular endothelial growth factor on endothelial cells. sFRP4 also selectively induced apoptotic events in endothelial cells by increasing cellular levels of reactive oxygen species. In vivo assays demonstrated a reduction in vascularity after sFRP4 treatment. Most importantly, sFRP4 restricted tumor growth in mice by interfering with endothelial cell function. The data demonstrate SFRP4 to be a potent angiogenesis inhibitor that warrants further investigation as a therapeutic agent in the control of angiogenesis-associated pathology. (Am J Pathol 2010, 176:1505-1516; DOI: 10.2353/ajpath.2010.090465)
Original languageEnglish
Pages (from-to)1505-1516
Number of pages12
JournalThe American Journal of Pathology: cellular and molecular biology of disease
Volume176
Issue number3
DOIs
Publication statusPublished - Mar 2010

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