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EMBO J. 2000 Apr 3;19(7):1525-33.

Identification of a peptide blocking vascular endothelial growth factor (VEGF)-mediated angiogenesis.

Author information

1
Université Paris XIII, UFR Léonard de Vinci, UPRES 2360, 'Ciblage Fonctionnel des Tumeurs Solides', 74 rue Marcel Cachin, 93017 Bobigny Cedex, France. tournair@unice.fr

Abstract

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.

PMID:
10747021
PMCID:
PMC310222
DOI:
10.1093/emboj/19.7.1525
[Indexed for MEDLINE]
Free PMC Article

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