The dynamic roles of angiopoietins in tumor angiogenesis.
Angiopoietin (Ang)-1 and -2, and mouse Ang-3/human Ang-4 are ligands of the receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Tie)-2. It is well established that the Ang-Tie-2 pathway is involved in tumor angiogenesis. However, the exact effects of angiopoietins on tumor angiogenesis are under debate. Experimental and clinical studies have demonstrated that increased expression of Ang-1 and -2 promotes or inhibits tumor angiogenesis, and correlates with a reduced or extended survival time of patients, and with a declined or improved clinical outcome. In general, these studies suggest that Ang-1 is a proangiogenic factor that promotes endothelial cell survival and tumor angiogenesis, especially in the presence of vascular endothelial growth factor; whereas Ang-2 destabilizes vasculature that leads to the initiation of angiogenesis or apoptosis of endothelial cells/vessel regression in the presence or absence of vascular endothelial growth factor, respectively, and that the cell-surface tethered Ang-3 displays antiangiogenic activity. Together, these results suggest that the Ang-Tie-2 functional axis is an attractive target for antiangiogenesis-based cancer therapy.
University of Pennsylvania, Department of Pathobiology, School of Veterinary Medicine, Philadelphia, PA 19104, USA. qyu@vet.upenn.edu
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D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D015398:Signal Transduction / Q000502:physiology*
D042682:Angiopoietins