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Identification of a peptide blocking vascular endothelial growth factor (VEGF)‐mediated angiogenesis
Author(s) -
BinétruyTournaire Roselyne,
Demangel Caroline,
Malavaud Bernard,
Vassy Roger,
Rouyre Sylvie,
Kraemer Michel,
Plouët Jean,
Derbin Claude,
Perret Gérard,
Mazié Jean Claude
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.7.1525
Subject(s) - angiogenesis , biology , vascular endothelial growth factor , kinase insert domain receptor , phage display , endothelial stem cell , cancer research , vascular endothelial growth factor a , receptor , peptide library , microbiology and biotechnology , peptide , in vitro , biochemistry , peptide sequence , vegf receptors , gene
Vascular endothelial growth factor (VEGF) binding to the kinase domain receptor (KDR/FLK1 or VEGFR‐2) mediates vascularization and tumor‐induced angiogenesis. Since there is evidence that KDR plays an important role in tumor angiogenesis, we sought to identify peptides able to block the VEGF–KDR interaction. A phage epitope library was screened by affinity for membrane‐expressed KDR or for an anti‐VEGF neutralizing monoclonal antibody. Both strategies led to the isolation of peptides binding KDR specifically, but those isolated by KDR binding tended to display lower reactivities. Of the synthetic peptides corresponding to selected clones tested to determine their inhibitory activity, ATWLPPR completely abolished VEGF binding to cell‐displayed KDR. In vitro , this effect led to the inhibition of the VEGF‐mediated proliferation of human vascular endothelial cells, in a dose‐dependent and endothelial cell type‐specific manner. Moreover, in vivo , ATWLPPR totally abolished VEGF‐induced angiogenesis in a rabbit corneal model. Taken together, these data demonstrate that ATWLPPR is an effective antagonist of VEGF binding, and suggest that this peptide may be a potent inhibitor of tumor angiogenesis and metastasis.