Vascular endothelial growth factor (VEGF) signaling in tumor progression.
Vascular endothelial cells are ordinarily quiescent in adult humans and divide less than once per decade. When tumors reach a size of about 0.2-2.0mm in diameter, they become hypoxic and limited in size in the absence of angiogenesis. There are about 30 endogenous pro-angiogenic factors and about 30 endogenous anti-angiogenic factors. In order to increase in size, tumors undergo an angiogenic switch where the action of pro-angiogenic factors predominates, resulting in angiogenesis and tumor progression. One mechanism for driving angiogenesis results from the increased production of vascular endothelial growth factor (VEGF) following up-regulation of the hypoxia-inducible transcription factor. The human VEGF family consists of VEGF (VEGF-A), VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). The VEGF family of receptors consists of three protein-tyrosine kinases and two non-protein kinase receptors (neuropilin-1 and -2). Owing to the importance of angiogenesis in tumor progression, inhibition of VEGF signaling represents an attractive cancer treatment.
Roskoski
Robert
R
Blue Ridge Institute for Medical Research, 3754 Brevard Road, Suite 116A, Box 19, Horse Shoe, NC 28742, USA. rrj@brimr.org
D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D039921:Neuropilins / Q000378:metabolism; D009857:Oncogenes / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D039921:Neuropilins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor