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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-7-31
pubmed:abstractText
Vascular endothelial growth factor (VEGF), a major factor mediating endothelial cell survival, migration, and proliferation during angiogenesis, is expressed as five splice variants (121, 145, 165, 189, and 206 aminoacids) encoded by a single gene. Although the three shorter isoforms are mainly diffusible, the two longer ones are sequestered in cell membranes after secretion. However, their potential role as true components of the extracellular matrix has not been investigated. We determined that endothelial cells could adhere and spread on VEGF189 and VEGF165, but not on VEGF121. Adhesion was mediated by the alpha3beta1 and alpha(v)beta3 integrins and other alpha(v) integrins but not by the cognate VEGF receptors. Cells migrated on VEGF165 and VEGF189 and displayed a stellate morphology with numerous lamellopodia and FAK staining but no actin stress fibers. Tumstatin, an antiangiogenic peptide that interacts with the alpha(v)beta3 integrin, could inhibit adhesion on VEGF, and this effect was potentiated by anti-alpha(v)beta3 blocking antibody. Immobilized VEGF almost totally abolished endothelial cell apoptosis through interactions with integrins. The inhibition of alpha(v)beta3 engagement with immobilized VEGF by tumstatin inhibited most of its survival activity. We have thus determined a new VEGF receptor-independent role for immobilized VEGF in supporting cell adhesion and survival through interactions with integrins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1520-2
pubmed:dateRevised
2007-5-2
pubmed:meshHeading
pubmed-meshheading:12709411-Cell Adhesion, pubmed-meshheading:12709411-Cell Movement, pubmed-meshheading:12709411-Cell Survival, pubmed-meshheading:12709411-Cells, Cultured, pubmed-meshheading:12709411-Endothelial Growth Factors, pubmed-meshheading:12709411-Endothelium, Vascular, pubmed-meshheading:12709411-Extracellular Matrix, pubmed-meshheading:12709411-Humans, pubmed-meshheading:12709411-Integrin alpha3beta1, pubmed-meshheading:12709411-Integrin alphaVbeta3, pubmed-meshheading:12709411-Integrins, pubmed-meshheading:12709411-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:12709411-Lymphokines, pubmed-meshheading:12709411-Models, Biological, pubmed-meshheading:12709411-Stress Fibers, pubmed-meshheading:12709411-Vascular Endothelial Growth Factor A, pubmed-meshheading:12709411-Vascular Endothelial Growth Factors
pubmed:year
2003
pubmed:articleTitle
Extracellular matrix-bound vascular endothelial growth factor promotes endothelial cell adhesion, migration, and survival through integrin ligation.
pubmed:affiliation
GDR CNRS 1927-Angiogenese and UMR CNRS 5089, Institut de Pharmacologie et Biologie Structurale, Toulouse, France.
pubmed:publicationType
Journal Article