Cytotoxicity of VEGF(121)/rGel on vascular endothelial cells resulting in inhibition of angiogenesis is mediated via VEGFR-2.

ABSTRACT:

Background

The fusion protein VEGF(121)/rGel composed of the growth factor VEGF(121) and the plant toxin gelonin targets the tumor neovasculature and exerts impressive anti-vascular effects. We have previously shown that VEGF(121)/rGel is cytotoxic to endothelial cells overexpressing VEGFR-2 but not to endothelial cells overexpressing VEGFR-1. In this study, we examined the basis for the specific toxicity of this construct and assessed its intracellular effects in vitro and in vivo.

Methods

We investigated the binding, cytotoxicity and internalization profile of VEGF(121)/rGel on endothelial cells expressing VEGFR-1 or VEGFR-2, identified its effects on angiogenesis models in vitro and ex vivo, and explored its intracellular effects on a number of molecular pathways using mi

SUBMITTER: Mohamedali KA 

PROVIDER: S-EPMC3176242 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature