Molecular regulation of the VEGF family -- inducers of angiogenesis and lymphangiogenesis.

The vascular endothelial growth factor (VEGF) family of secreted glycoproteins are critical inducers of angiogenesis (growth of blood vessels) and lymphangiogenesis (growth of lymphatic vessels). These proteins are attractive therapeutic targets for blocking growth of blood vessels and lymphatics in tumors and thereby inhibiting the growth and spread of cancer -- in fact, the first VEGF inhibitor has recently entered the clinic for treatment of cancer. In addition, the VEGFs are being considered for stimulation of angiogenesis in the context of ischemic disease and lymphangiogenesis for treatment of lymphedema. These therapeutic possibilities have focused great interest on the molecular regulation of VEGF family members. Much has been learned in the past five years about the mechanisms controlling the action of the VEGFs, including the importance of hypoxia, proteolysis, transcription factors and RNA splicing. An understanding of these mechanisms offers broader opportunities to manipulate expression and activity of the VEGFs for treatment of disease.