Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Oncogene ; 36(47): 6531-6541, 2017 11 23.
Article in English | MEDLINE | ID: mdl-28783175

ABSTRACT

Vascular endothelial growth factor receptor-2 (VEGFR2) is the main pro-angiogenic receptor expressed by endothelial cells (ECs). Using surface plasmon resonance, immunoprecipitation, enzymatic digestion, immunofluorescence and cross-linking experiments with specific sugar-binding lectins, we demonstrated that VEGFR2 bears both α,1-fucose and α(2,6)-linked sialic acid (NeuAc). However, only the latter is required for VEGF binding to VEGFR2 and consequent VEGF-dependent VEGFR2 activation and motogenic response in ECs. Notably, downregulation of ß-galactoside α(2,6)-sialyltransferase expression by short hairpin RNA transduction inhibits VEGFR2 α(2,6) sialylation that is paralleled by an increase of ß-galactoside α(2,3)-sialyltransferase expression. This results in an ex-novo α(2,3)-NeuAc sialylation of the receptor that functionally replaces the lacking α(2,6)-NeuAc, thus allowing VEGF/VEGFR2 interaction. In keeping with the role of VEGFR2 sialylation in angiogenesis, the α(2,6)-NeuAc-binding lectin Sambucus nigra (SNA) prevents VEGF-dependent VEGFR2 autophosphorylation and EC motility, proliferation and motogenesis. In addition, SNA exerts a VEGF-antagonist activity in tridimensional angiogenesis models in vitro and in the chick-embryo chorioallantoic membrane neovascularization assay and mouse matrigel plug assay in vivo. In conclusion, VEGFR2-associated NeuAc plays an important role in modulating VEGF/VEGFR2 interaction, EC pro-angiogenic activation and neovessel formation. VEGFR2 sialylation may represent a target for the treatment of angiogenesis-dependent diseases.


Subject(s)
Neovascularization, Pathologic/metabolism , Plant Lectins/pharmacology , Protein Processing, Post-Translational , Ribosome Inactivating Proteins/pharmacology , Vascular Endothelial Growth Factor Receptor-2/metabolism , Animals , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Chick Embryo , Chorioallantoic Membrane , Down-Regulation , Endothelial Cells/metabolism , Female , Fluorescent Antibody Technique , Galactosides , Human Umbilical Vein Endothelial Cells , Humans , Mice , Mice, Inbred C57BL , N-Acetylneuraminic Acid/metabolism , Neovascularization, Physiologic , Phosphorylation/drug effects , RNA, Small Interfering , Sialyltransferases/genetics , Sialyltransferases/metabolism , Surface Plasmon Resonance , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism , beta-D-Galactoside alpha 2-6-Sialyltransferase , beta-Galactoside alpha-2,3-Sialyltransferase
SELECTION OF CITATIONS
SEARCH DETAIL
...