Regulation of endothelial cell integrin function and angiogenesis by COX-2, cAMP and Protein Kinase A.

Details

Serval ID
serval:BIB_7BA701A9D625
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Regulation of endothelial cell integrin function and angiogenesis by COX-2, cAMP and Protein Kinase A.
Journal
Thrombosis and Haemostasis
Author(s)
Dormond O., Rüegg C.
ISSN
0340-6245 (Print)
ISSN-L
0340-6245
Publication state
Published
Issued date
2003
Volume
90
Number
4
Pages
577-585
Language
english
Abstract
Angiogenesis, the development of new blood vessels from preexisting vessels, is a key step in tumor growth, invasion and metastasis formation. Inhibition of tumor angiogenesis is considered as an attractive approach to suppress cancer progression and spreading. Adhesion receptors of the integrin family promote tumor angiogenesis by mediating cell migration, proliferation and survival of angiogenic endothelial cells. Integrins up regulated and highly expressed on neovascular endothelial cells, such as alphaVbeta3 and alpha5beta1, have been considered as relevant targets for anti-angiogenic therapies. Small molecular integrin antagonists or blocking antibodies suppress angiogenesis and tumor progression in many animal models, and some of them are currently being tested in cancer clinical trials as anti-angiogenic agents. COX-2 inhibitors exert anti-cancer effects, at least in part, by inhibiting tumor angiogenesis. We have recently shown that COX-2 inhibitors suppress endothelial cell migration and angiogenesis by preventing alphaVbeta3-mediated and cAMP/PKA-dependent activation of the small GTPases Rac and Cdc42. Here we will review the evidence for the involvement of vascular integrins in mediating angiogenesis and the role of COX-2 metabolites in modulating the cAMP/Protein Kinase A pathway and alphaVbeta3-dependent Rac activation in endothelial cells.
Keywords
Cyclic AMP/pharmacology, Cyclic AMP-Dependent Protein Kinases/pharmacology, Cyclooxygenase 2, Endothelium, Vascular/cytology, Endothelium, Vascular/physiology, Humans, Integrins/drug effects, Integrins/physiology, Isoenzymes/pharmacology, Membrane Proteins, Neoplasms/blood supply, Neovascularization, Pathologic, Prostaglandin-Endoperoxide Synthases/pharmacology
Pubmed
Web of science
Create date
28/01/2008 8:36
Last modification date
20/08/2019 14:37
Usage data