[PDF][PDF] Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis
Cancer cell, 2004•cell.com
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 …
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 …
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.
cell.com