|
|
Blood, 1 March 2008, Vol. 111, No. 5, pp. 2674-2680.
Prepublished online as a Blood First Edition Paper on January 7, 2008; DOI 10.1182/blood-2007-08-110205.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Semaphorin 3A suppresses VEGF-mediated angiogenesis yet acts as a vascular permeability factor
Lisette M. Acevedo1,
Samuel Barillas1,
Sara M. Weis1,
Joachim R. Göthert2, and
David A. Cheresh1
1 Department of Pathology and Moores UCSD Cancer Center, University of California, San Diego, La Jolla; and
2 Department of Hematology, University Hospital, Essen, Germany
Semaphorin 3A (Sema3A), a known inhibitor of axonal sprouting, also alters vascular patterning. Here we show that Sema3A selectively interferes with VEGF- but not bFGF-induced angiogenesis in vivo. Consistent with this, Sema3A disrupted VEGF- but not bFGF-mediated endothelial cell signaling to FAK and Src, key mediators of integrin and growth factor signaling; however, signaling to ERK by either growth factor was unperturbed. Since VEGF is also a vascular permeability (VP) factor, we examined the role of Sema3A on VEGF-mediated VP in mice. Surprisingly, Sema3A not only stimulated VEGF-mediated VP but also potently induced VP in the absence of VEGF. Sema3A-mediated VP was inhibited either in adult mice expressing a conditional deletion of endothelial neuropilin-1 (Nrp-1) or in wild-type mice systemically treated with a function-blocking Nrp-1 antibody. While both Sema3A- and VEGF-induced VP was Nrp-1 dependent, they use distinct downstream effectors since VEGF- but not Sema3A-induced VP required Src kinase signaling. These findings define a novel role for Sema3A both as a selective inhibitor of VEGF-mediated angiogenesis and a potent inducer of VP.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
P. Gaur, D. R. Bielenberg, S. Samuel, D. Bose, Y. Zhou, M. J. Gray, N. A. Dallas, F. Fan, L. Xia, J. Lu, et al.
Role of Class 3 Semaphorins and Their Receptors in Tumor Growth and Angiogenesis
Clin. Cancer Res.,
November 15, 2009;
15(22):
6763 - 6770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Teesalu, K. N. Sugahara, V. R. Kotamraju, and E. Ruoslahti
C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration
PNAS,
September 22, 2009;
106(38):
16157 - 16162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. K. McLoon
A new role for satellite cells: control of reinnervation after muscle injury by semaphorin 3A. Focus on "Possible implication of satellite cells in regenerative motoneuritogenesis: HGF upregulates neural chemorepellent Sema3A during myogenic differentiation"
Am J Physiol Cell Physiol,
August 1, 2009;
297(2):
C227 - C230.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Capparuccia and L. Tamagnone
Semaphorin signaling in cancer cells and in cells of the tumor microenvironment - two sides of a coin
J. Cell Sci.,
June 1, 2009;
122(11):
1723 - 1736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Serini, L. Napione, M. Arese, and F. Bussolino
Besides adhesion: new perspectives of integrin functions in angiogenesis
Cardiovasc Res,
May 1, 2008;
78(2):
213 - 222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
