Author/Authors :
Tang، نويسنده , , Nan and Wang، نويسنده , , Lianchun and Esko، نويسنده , , Jeffrey and Giordano، نويسنده , , Frank J. and Huang، نويسنده , , Yan and Gerber، نويسنده , , Hans-Peter and Ferrara، نويسنده , , Napoleone and Johnson، نويسنده , , Randall S.، نويسنده ,
Abstract :
We deleted the hypoxia-responsive transcription factor HIF-1α in endothelial cells (EC) to determine its role during neovascularization. We found that loss of HIF-1α inhibits a number of important parameters of EC behavior during angiogenesis: these include proliferation, chemotaxis, extracellular matrix penetration, and wound healing. Most strikingly, loss of HIF-1α in EC results in a profound inhibition of blood vessel growth in solid tumors. These phenomena are all linked to a decreased level of VEGF expression and loss of autocrine response of VEGFR-2 in HIF-1α null EC. We thus show that a HIF-1α-driven, VEGF-mediated autocrine loop in EC is an essential component of solid tumor angiogenesis.
