A peptide mimicking the binding sites of VEGF-A and VEGF-B inhibits VEGFR-1/-2 driven angiogenesis, tumor growth and metastasis.

ABSTRACT: Interfering with interactions of vascular endothelial growth factors (VEGFs) with their receptors (VEGFRs) effectively inhibits angiogenesis and tumor growth. We designed an antagonist peptide of VEGF-A and VEGF-B reproducing two discontinuous receptor binding regions of VEGF-B (loop 1 and loop3) covalently linked together by a receptor binding region of VEGF-A (loop3). The designed peptide (referred to as VGB4) was able to bind to both VEGFR1 and VEGFR2 on the Human Umbilical Vein Endothelial Cells (HUVECs) surface and inhibited VEGF-A driven proliferation, migration and tube formation in HUVECs through suppression of ERK1/2 and AKT phosphorylation. The whole-animal fluorescence imaging demonstrated that fluorescein isothiocyanate (FITC)-VGB4 accumulated in the mammary carcinoma tumors (M

SUBMITTER: Farzaneh Behelgardi M 

PROVIDER: S-EPMC6298961 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature