Secreted frizzled-related protein 4: An angiogenesis inhibitor

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 vit...

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Main Authors: Muley, A., Majumder, S., Kolluru, G., Parkinson, S., Viola, H., Hool, L., Arfuso, Frank, Ganss, R., Dharmarajan, Arunasalam, Chatterjee, S.
Format: Journal Article
Published: Elsevier Inc. 2010
Online Access:http://hdl.handle.net/20.500.11937/5075
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author Muley, A.
Majumder, S.
Kolluru, G.
Parkinson, S.
Viola, H.
Hool, L.
Arfuso, Frank
Ganss, R.
Dharmarajan, Arunasalam
Chatterjee, S.
author_facet Muley, A.
Majumder, S.
Kolluru, G.
Parkinson, S.
Viola, H.
Hool, L.
Arfuso, Frank
Ganss, R.
Dharmarajan, Arunasalam
Chatterjee, S.
author_sort Muley, A.
building Curtin Institutional Repository
collection Online Access
description 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/ß-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. Copyright © American Society for Investigative Pathology.
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spelling curtin-20.500.11937-50752018-03-29T09:05:23Z Secreted frizzled-related protein 4: An angiogenesis inhibitor Muley, A. Majumder, S. Kolluru, G. Parkinson, S. Viola, H. Hool, L. Arfuso, Frank Ganss, R. Dharmarajan, Arunasalam Chatterjee, S. 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/ß-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. Copyright © American Society for Investigative Pathology. 2010 Journal Article http://hdl.handle.net/20.500.11937/5075 10.2353/ajpath.2010.090465 Elsevier Inc. restricted
spellingShingle Muley, A.
Majumder, S.
Kolluru, G.
Parkinson, S.
Viola, H.
Hool, L.
Arfuso, Frank
Ganss, R.
Dharmarajan, Arunasalam
Chatterjee, S.
Secreted frizzled-related protein 4: An angiogenesis inhibitor
title Secreted frizzled-related protein 4: An angiogenesis inhibitor
title_full Secreted frizzled-related protein 4: An angiogenesis inhibitor
title_fullStr Secreted frizzled-related protein 4: An angiogenesis inhibitor
title_full_unstemmed Secreted frizzled-related protein 4: An angiogenesis inhibitor
title_short Secreted frizzled-related protein 4: An angiogenesis inhibitor
title_sort secreted frizzled-related protein 4: an angiogenesis inhibitor
url http://hdl.handle.net/20.500.11937/5075