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VEGF plays a central role throughout tumor development

Vascular endothelial growth factor (VEGF) contributes to tumor growth in several important ways^1-8:

Facilitates survival of existing vessels
Contributes to vascular abnormalities (eg, high interstitial pressure) that my impede effective delivery of antitumor compounds
Stimulates new vessel growth
May prevent immune response to tumors

The mechanisms from which the various functions of VEGF in endothelial cells arise are shown in the table below.

Function	Mechanism
Proliferation	Activation of mitogen-activated protein kinases
Permeability	Vesicovascular organelles Endothelial fenestrations Opening of junctions between adjacent endothelial cells
Invasion	Induction of metalloproteinases uPA, uPAR, TTPA
Migration	Activation of FAK, p38, nitric oxide
Survival	Induction of PI3K/Akt, Bcl2, A1, survivin, XIAP, or FAK Inhibition of caspases
Activation	Upregulation of integrin expression Alteration of cell cytoskeleton

Abbreviations: uPA, urokinase-type plasminogen activator; uPAR, uPA receptor; TTPA, tissue-type plasminogen activator.²

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Gabrilovich DI, Chen HL, Girgis KR, et al. Nat Med. 1996;2:1096-1103.; 8.

Barbera-Guillem E, Nyhus JK, Wolford CC, Friece CR, Sampsel JW. Cancer Res. 2002;62:7042-7049.; 9.

Ferrara N, Carver-Moore K, Chen H, et al. Nature. 1996;380:439-442.; 10.

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