Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells

We identify a novel function for the vascular endothelial growth factor (VE GF) in its ability to stimulate an autocrine signaling pathway in metastati c breast carcinoma cells that is essential for their survival. Suppression of VEGF expression in metastatic cells in vitro induced their apoptosis, in addition to inhibiting the constitutively elevated phosphatidylinositol 3 ' -kinase activity that is characteristic of these cells and important for their survival. Hypoxia enhanced the survival of metastatic cells by increa sing VEGF expression. The importance of the VEGF receptor neuropilin was in dicated by the ability of a neuropilin-binding VEGF isoform to enhance brea st carcinoma survival. Moreover, the expression of neuropilin in neuropilin -deficient breast carcinoma cells protected them from apoptosis. The identi fication of this VEGF autocrine signaling pathway has important implication s for tumor metastasis and therapeutic intervention.