Abstract: Tie2 was identified as a receptor tyrosine kinase (RTK) expressed principally on vascular endothelium. Disrupting Tie2 function in mice resulted in embryonic lethality with defects in embryonic vasculature. Multiple ligands for Tie2, named angiopoietin (Ang), have been identified. Ang1, an agonist, stimulates Tie2 phosphorylation in endothelial cells (EC). Ang2 has been considered to be an antagonist of Tie2 that blocks Tie2 activation induced by Ang1 in EC. Disrupting the function of Ang1 or overproduction of Ang2 yielded a phenotype similar to the Tie2 knockout, confirming the importance of the Ang/Tie2 pathway during embryonic vascular development. The genetic evidence suggests that the VEGF pathway and the Tie2 pathway seem to work in a complementary and coordinated fashion during vascular development. Many clinical and animal studies show critical roles of Ang/Tie2 pathway in tumor angiogenesis. The interaction of the Ang/Tie2 pathway with the VEGF pathway has also been demonstrated. Elevated VEGF and Ang2 expressions are associated with increased tumor angiogenesis. Ang2 corresponds positively with tumor development and progression as well as with metastasis and correlates negatively with patient survival in many studies. Blocking the Ang/Tie2 pathway has been shown to inhibit tumor angiogenesis, growth, and metastasis, demonstrating the potential of future clinical therapies based on this pathway. As anti-angiogenic therapies move from the bench to a clinical setting, an understanding of the role of the Ang/Tie2 pathway is vital.
Publication Year: 2008
Publication Date: 2008-01-04
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 2
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