VEGF plays a central role throughout tumor development

Vascular endothelial growth factor (VEGF) contributes to tumor growth in several important ways3,4,6-9,58,59:

  • 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.

Summary of VEGF functions on endothelial cells60,61

FunctionMechanism
ProliferationActivation of mitogen-activated protein kinases
PermeabilityVesicovascular organelles
Endothelial fenestrations
Opening of junctions between adjacent endothelial cells
InvasionInduction of metalloproteinases uPA, uPAR, TTPA
MigrationActivation of FAK, p38, nitric oxide
SurvivalInduction of PI3K/Akt, Bcl2, A1, survivin, XIAP, or FAK
Inhibition of caspases
ActivationUpregulation of integrin expression
Alteration of cell cytoskeleton

Abbreviations: uPA, urokinase-type plasminogen activator; uPAR, uPA receptor; TTPA, tissue-type plasminogen activator.4

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