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Among the many factors implicated in angiogenesis, VEGF has been identified as the most potent and predominant. The scope of scientific research involving VEGF continues to grow exponentially. From 1995 to 2005, the number of VEGF-related abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) increased 50-fold, highlighting the increased focus in research upon VEGF's role in oncology.
VEGF (also known as VEGF-A, but commonly referred to simply as VEGF) stands for “vascular endothelial growth factor.” This protein plays an important role in angiogenesis. As its name suggests, VEGF stimulates vascular endothelial cell growth, survival, and proliferation. As seen in preclinical models, VEGF has been shown to facilitate survival of existing vessels, contribute to vascular abnormalities (eg, tortuousness and hyperpermeability) that may impede effective delivery of antitumor compounds, and stimulate new vessel growth.3,4,6-9
VEGF is a member of a family of 6 structurally related proteins (see table below) that regulate the growth and differentiation of multiple components of the vascular system, especially blood and lymph vessels. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2.3,4,10,11
| VEGF Family Members | Receptors | Functions |
| VEGF (VEGF-A) | VEGFR-1, VEGFR-2, neuropilin-1 | Angiogenesis Vascular maintenance |
| VEGF-B | VEGFR-1 | Not established |
| VEGF-C | VEGFR-2, VEGFR-3 | Lymphangiogenesis |
| VEGF-D | VEGFR-2, VEGFR-3 | Lymphangiogenesis |
| VEGF-E (viral factor) | VEGFR-2 | Angiogenesis |
| Placental growth factor (PlGF) | VEGFR-1, neuropilin-1 | Angiogenesis Inflammation |
There are 4 major isoforms of VEGFA (VEGF), each coded for by a different portion of the VEGF gene. These isoforms are VEGF121, VEGF165, VEGF189, and VEGF206. Although these isoforms behave identically in solution, they differ in their ability to bind heparin and the extracellular matrix.12
