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Type: Journal article
Title: Syndecan-1 regulates αvβ₃ and αvβ₅ integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor
Other Titles: Syndecan-1 regulates alpha(v) beta(3) and alpha(v) beta(5) integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor
Author: Beauvais, D.
Ell, B.
McWhorter, A.
Rapraeger, A.
Citation: Journal of Experimental Medicine, 2009; 206(3):691-705
Publisher: Rockefeller University Press
Issue Date: 2009
ISSN: 0022-1007
Statement of
DeannaLee M. Beauvais , Brian J. Ell , Andrea R. McWhorter , and Alan C. Rapraeger
Abstract: Syndecan-1 (Sdc1) is a matrix receptor shown to associate via its extracellular domain with the alpha(v)beta(3) and alpha(v)beta(5) integrins, potentially regulating cell adhesion, spreading, and invasion of cells expressing these integrins. Using Sdc1 deletion mutants expressed in human mammary carcinoma cells, we identified the active site within the Sdc1 core protein and derived a peptide inhibitor called synstatin (SSTN) that disrupts Sdc1's interaction with these integrins. Because the alpha(v)beta(3) and alpha(v)beta(5) integrins are critical in angiogenesis, a process in which a role for Sdc1 has been uncertain, we used human vascular endothelial cells in vitro to show that the Sdc1 regulatory mechanism is also required for integrin activation on these cells. We found Sdc1 expressed in the vascular endothelium during microvessel outgrowth from aortic explants in vitro and in mouse mammary tumors in vivo. Moreover, we show that SSTN blocks angiogenesis in vitro or when delivered systemically in a mouse model of angiogenesis in vivo, and impairs mammary tumor growth in an orthotopic mouse tumor model. Thus, Sdc1 is a critical regulator of these two important integrins during angiogenesis and tumorigenesis, and is inhibited by the novel SSTN peptide.
Keywords: Aorta
Endothelium, Vascular
Cell Line, Tumor
Breast Neoplasms
Fibroblast Growth Factors
Integrin alphaVbeta3
Receptors, Vitronectin
Cell Proliferation
Neovascularization, Physiologic
In Vitro Techniques
Rights: © 2009 Beauvais et al.
DOI: 10.1084/jem.20081278
Appears in Collections:Animal and Veterinary Sciences publications
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