Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin alphavbeta3 on vascular endothelial cells.
Vascular smooth muscle cell growth-promoting factor (VSGP) was originally isolated from bovine ovarian follicular fluid as a stimulator of vascular smooth muscle cell proliferation. Homology searches indicate that bovine and human VSGPs are orthologs of rat F-spondin. Here, we examined whether recombinant human VSGP/F-spondin affected the biological activities of endothelial cells. VSGP/F-spondin did not affect the proliferation of human umbilical vein endothelial cells (HUVECs); however, it did inhibit VEGF- or bFGF-stimulated HUVEC migration. To clarify the mechanism of this inhibitory effect, we examined the adhesion of HUVECs to extracellular matrix proteins. VSGP/F-spondin specifically inhibited the spreading of HUVECs on vitronectin via the functional blockade of integrin alphavbeta3. As a result, VSGP/F-spondin inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) when HUVECs were plated on vitronectin. Moreover, VSGP/F-spondin inhibited the activation of Akt when HUVECs on vitronectin were stimulated with VEGF. VSGP/F-spondin inhibited tube formation by HUVECs in vitro and neovascularization in the rat cornea in vivo. These results indicate that VSGP/F-spondin inhibits angiogenesis at least in part by the blockade of endothelial integrin alphavbeta3.
Terai
Y
Y
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Abe
M
M
Miyamoto
K
K
Koike
M
M
Yamasaki
M
M
Ueda
M
M
Ueki
M
M
Sato
Y
Y
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007424:Intracellular Fluid / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000494:pharmacology*; D010455:Peptides; D051381:Rats; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019006:Neural Cell Adhesion Molecules; D010455:Peptides; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C429104:SPON1 protein, human; C498955:Spon1 protein, rat; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors