VEGF-Integrin Interplay Controls Tumor Growth and Vascularization

Cross-talk between the major angiogenic growth factor, VEGF, and integrin cell adhesion receptors has emerged recently as a critical factor in the regulation of angiogenesis and tumor development. However, the molecular mechanisms and consequences of this intercommunication remain unclear. Here, we...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-05, Vol.102 (21), p.7589-7594
Main Authors: De, Sarmishtha, Razorenova, Olga, McCabe, Noel Patrick, O'Toole, Timothy, Qin, Jun, Byzova, Tatiana V., Stark, George R.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Angiogenesis
Animals
Antibodies
Biological Sciences
Blood vessels
Cell growth
Cell Line, Tumor
Cell lines
Cell Movement - physiology
Cellular biology
Enzyme-Linked Immunosorbent Assay
Gene expression
Humans
Immunoblotting
Immunoprecipitation
Integrin alphaVbeta3 - metabolism
Integrin beta3 - genetics
Integrins
Ligands
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred Strains
Mutation - genetics
Neoplasms - metabolism
Neovascularization, Pathologic - metabolism
Phosphorylation
Plasmids - genetics
Shc Signaling Adaptor Proteins
Src Homology 2 Domain-Containing, Transforming Protein 1
Tumor cell line
Tumors
Vascular Endothelial Growth Factor A - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cross-talk between the major angiogenic growth factor, VEGF, and integrin cell adhesion receptors has emerged recently as a critical factor in the regulation of angiogenesis and tumor development. However, the molecular mechanisms and consequences of this intercommunication remain unclear. Here, we define a mechanism whereby integrin αvβ3, through activation, clustering, and signaling by means of p66 Shc (Src homology 2 domain containing), regulates the production of VEGF in tumor cells expressing this integrin. Tumors with "activatable" but not "inactive" β3 integrin secrete high levels of VEGF, which in turn promotes extensive neovascularization and augments tumor growth in vivo. This stimulation of VEGF expression depends upon the ability of αvβ3 integrin to cluster and promote phosphorylation of p66 Shc. These observations identify a link between β3 integrins and VEGF in tumor growth and angiogenesis and, therefore, may influence anti-integrin as well as anti-VEGF therapeutic strategies.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0502935102