Vascular endothelial growth factor receptors: expression and function in solid tumors

Abstract

Vascular endothelial growth factor (VEGF) and its family members are important mediators of tumor angiogenesis. The multiple functions of the VEGF are mediated through complex and selective interactions between the ligands, their high-affinity tyrosine kinase receptors, and co-receptors (neuropilins). While these receptors are historically described as being exclusively expressed on endothelial cells, emerging evidence has documented expression of these receptors on a number of nonendothelial cells, including tumor cells. The VEGF receptors (VEGFR) have also been shown to be functional in a number of nonendothelial systems, where they may be targets for anti-VEGF therapy. This article will review the basic effects and interactions of the VEGFRs on endothelial cells and the evidence for their expression and function on tumor cells. The novel expression of VEGFRs on tumor cells contributes to the understanding of the complex roles of VEGF within the tumor microenvironment, potentially affecting both endothelial cells and tumor cells expressing the VEGFRs. This elucidation of VEGF activity may further refine antineoplastic regimens for solid malignancies.