VEGF: a predominant mediator of angiogenesis

What is VEGF?

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. Among the many factors implicated in angiogenesis, VEGF has been identified as one of the most potent and predominant. 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.^1-6

The structure of VEGF

This ribbon representation shows a dimerized VEGF/VEGF receptor complex, as observed by X-ray crystallography. Two monomers of VEGF (blue and yellow) are shown bound to domain 2 of the VEGFR-1 receptor (green).¹

Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25(4):581-611. © 2004 The Endocrine Society.

The VEGF family of proteins

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.^1,2,7,8

There are 4 major isoforms of VEGF_A (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.⁹

References:

1.

Ferrara N. Endocr Rev. 2004;25:581-611. PMID: 15294883

2.

Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027. PMID: 15585754

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Bergers G, Benjamin LE. Nat Rev Cancer. 2003;3:401-410. PMID: 12778130

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Jain RK. Nat Med. 2001;7:987-989. PMID: 11533692

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Jain RK. Science. 2005;307:58-62. PMID: 15637262

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Gerber HP, Ferrara N. Cancer Res. 2005;65:671-680. PMID: 15705858

7.

Relf M, LeJeune S, Scott PAE, et al. Cancer Res. 1997;57:963-969. PMID: 9041202

8.

Stimpfl M, Tong D, Fasching B, et al. Clin Cancer Res. 2002;8:2253-2259. PMID: 12114428

9.

Relf M, LeJeune S, Scott PAE, et al. Cancer Res. 1997;57:963-969. PMID: 9041202