Endothelial cell survival and apoptosis in the tumor vasculature

Angiogenesis is essential for the growth and metastasis of solid tumors. Th e balance of endothelial cell (EC) proliferation and apoptosis is a major d eterminant in tumor angiogenesis. Recently, several studies demonstrated th at numerous angiogenic factors not only induce angiogenesis but also functi on as EC survival factors. Vascular endothelial growth factor (VEGF), a pot ent angiogenic factor, is also an EC survival factor in embryonic vasculoge nesis and tumor angiogenesis. VEGF activates specific intracellular surviva l pathways in ECs including Bcl-2, A1, IAP, Akt, and Erk. Integrins may fun ction as EC survival factors by preventing anoikis by enhancing binding to the extracellular matrix. In addition, integrins may function in concert wi th VEGF to promote EC survival. Angiopoietin-1 (Ang-1) has recently been sh own to stabilize EC networks by binding to the EC-specific tyrosine kinase receptor Tie-2. Pericytes also function as EC survival factors, by cell-cel l contact, secretion of survival factors, or both. Targeting any of the abo ve mechanisms for EC survival may provide novel antineoplastic strategies.