FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition.
Angiogenic growth factors such as fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs) are currently targets of intense efforts to inhibit deregulated blood vessel formation in diseases such as cancer. FGFs and VEGFs exert their effects via specific binding to cell surface-expressed receptors equipped with tyrosine kinase activity. Activation of the receptor kinase activity allows coupling to downstream signal transduction pathways that regulate proliferation, migration and differentiation of endothelial cells. Inhibitors of FGF and VEGF signalling are currently in clinical trials. In this article, the current knowledge of FGF- and VEGF-induced signal transduction that leads to specific biological responses will be summarized. Furthermore, the manner in which this knowledge is being exploited to regulate angiogenesis will be discussed.
Dept of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsväg 20, 751 85, Uppsala, Sweden. michael.cross@genpat.uu.se
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Cross
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Claesson-Welsh
D001665:Binding Sites; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors