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Secreted Frizzled-Related Protein 4: An Angiogenesis Inhibitor

Ajit Muley; Syamantak Majumder; Gopi Krishna Kolluru; Steve Parkinson; Helena Viola; Livia Hool; Frank Arfuso; Ruth Ganss; Arun Dharmarajan; Suvro Chatterjee

Title:
Secreted Frizzled-Related Protein 4: An Angiogenesis Inhibitor
Author(s):
Muley, Ajit
Majumder, Syamantak
Kolluru, Gopi Krishna
Parkinson, Steve
Viola, Helena
Hool, Livia
Arfuso, Frank
Ganss, Ruth
Dharmarajan, Arun
Chatterjee, Suvro
Date:
Type:
Articles
Department(s):
Obstetrics and Gynecology
Volume:
176
Persistent URL:
Book/Journal Title:
The American Journal of Pathology
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/β-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.
Subject(s):
Neovascularization inhibitors
Wnt proteins
Endothelial cells
Pathology
Publisher DOI:
https://doi.org/10.2353/ajpath.2010.090465
Item views
16
Metadata:
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Suggested Citation:
Ajit Muley, Syamantak Majumder, Gopi Krishna Kolluru, Steve Parkinson, Helena Viola, Livia Hool, Frank Arfuso, Ruth Ganss, Arun Dharmarajan, Suvro Chatterjee, , Secreted Frizzled-Related Protein 4: An Angiogenesis Inhibitor, Columbia University Academic Commons, .

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