VASCULAR-PERMEABILITY FACTOR, TUMOR ANGIOGENESIS AND STROMA GENERATION

Vascular permeability factor (VPF/VEGF) is a highly conserved multifun ctional cytokine that acts directly on endothelial cells (ECs) to acti vate phospholipase C and induce [Ca2+](i) transients. Two high-affinit y receptors, both tyrosine kinases, have been described. VPF/VEGF has at least two important roles in tumor biology: (1) it potently increas es microvascular permeability to plasma proteins, thereby modifying th e tumor extracellular matrix to promote the ingrowth of fibroblasts an d new blood vessels, and (2) it is a selective EC mitogen. VPF/VEGF is also involved in several other nonmalignant processes with a pathogen esis analogous to that of tumor stroma generation, including wound hea ling and rheumatoid arthritis.