Antiangiogenic therapy targeting factors that enhance endothelial cell survival

Abstract

The process of angiogenesis involves the formation of new blood vessels from established vasculature and the maintenance of the fragile neovascular network. Recent studies have shown that several angiogenic factors not only induce angiogenesis but also act as endothelial cell (EC) survival factors. Vascular endothelial growth factor, a potent angiogenic factor, is also an EC survival factor via activation of EC-specific tyrosine kinase receptors. Angiopoietin-1 has recently been shown to stabilize EC networks by binding to the EC-specific tyrosine kinase receptor Tie-2; in contrast, angiopoietin-2 is antagonistic to angiopoietin-1 and destabilizes EC networks. Integrins may function as EC survival factors by preventing apoptosis by numerous mechanisms mediated by binding to the extracellular matrix. Integrins may also function in concert with vascular endothelial growth factor to promote EC survival. Lastly, pericytes contribute to EC stabilization by cell-cell contact and/or secretion of survival factors, such as vascular endothelial growth factor. Targeting EC survival factors may provide a novel antineoplastic strategy for cancer.