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Extracellular matrix‐bound vascular endothelial growth factor promotes endothelial cell adhesion, migration, and survival through integrin ligation
Author(s) -
Hutchings Helen,
Ortega Nathalie,
Plouët Jean
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0691fje
Subject(s) - integrin , microbiology and biotechnology , angiogenesis , vascular endothelial growth factor , extracellular matrix , endothelial stem cell , vascular endothelial growth factor a , biology , vascular endothelial growth factor c , cell adhesion , chemistry , cell , cancer research , biochemistry , vegf receptors , in vitro
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 VEGF 189 and VEGF 165 , but not on VEGF 121 . Adhesion was mediated by the α3β1 and αvβ3 integrins and other αv integrins but not by the cognate VEGF receptors. Cells migrated on VEGF 165 and VEGF 189 and displayed a stellate morphology with numerous lamellopodia and FAK staining but no actin stress fibers. Tumstatin, an antiangiogenic peptide that interacts with the αvβ3 integrin, could inhibit adhesion on VEGF, and this effect was potentiated by anti‐αvβ3 blocking antibody. Immobilized VEGF almost totally abolished endothelial cell apoptosis through interactions with integrins. The inhibition of αvβ3 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.