Premium
Induction of angiogenesis in vitro by vanadate, an inhibitor of phosphotyrosine phosphatases
Author(s) -
Montesano R.,
Pepper M. S.,
Belin D.,
Vassalli J.D.,
Orci L.
Publication year - 1988
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041340318
Subject(s) - vanadate , phosphorylation , angiogenesis , fibroblast growth factor , tyrosine phosphorylation , microbiology and biotechnology , protein tyrosine phosphatase , endothelial stem cell , phosphatase , biochemistry , fibroblast , tyrosine , biology , chemistry , in vitro , cancer research , receptor
We have previously shown that capillary endothelial cells grown on the surface of three‐dimensional collagen gels can be induced to invade the underlying fibrillar matrix and to form capillary‐like tubular structures in response to tumor‐promoting phorbol esters or the angiogenic agent fibroblast growth factor (FGF). Since both phorbol esters and FGF stimulate phosphorylation of tyrosine residues, we treated endothelial cells with vanadate, an inhibitor of phosphotyrosine‐specific phosphatases, to determine whether this agent could induce the expression of an anglogenic phenotype in these cells. We show here that vanadate stimulates endothelial cells to invade collagen matrices and to organize into characteristic tubules resembling those induced by FGF or phorbol esters. We have further observed that vanadate concomitantly stimulates endothelial cells to produce plasrninogen activators (PAs), proteolytic enzymes which are induced by phorbol esters and FGF, and which have been implicated in the neovascular response; this stimulation can be accounted for by an increase in the levels of urokinase‐type PA and tissue type PA mRNA. These results suggest a role for tyrosine phosphorylation in the regulation of the angiogenic phenotype in capillary endothelial cells.