Abstract |
Tie-1 and Tie-2 tyrosine kinase receptors are expressed specifically on vascular endothelial cells and on a certain subtype of macrophages implicated in angiogenesis, thus, they have been a major focus of angiogenesis research. Tie-1 and Tie-2 are essential for vascular maturation during developmental, physiological and pathological angiogenesis. Angiopoietin 1-4 (Ang-1-4) have been identified as bona fide ligands of the Tie-2 receptor, while Tie-1 remains an orphan receptor which is able to heterodimerize with Tie-2 and to modulate Tie-2 signal transduction. The most exhaustively studied angiopoietins are Ang-1 and Ang-2. Ang-1 is a critical player in vessel maturation and it mediates migration, adhesion and survival of endothelial cells. Ang-2 disrupts the connections between the endothelium and perivascular cells and promotes cell death and vascular regression. Yet, in conjunction with VEGF, Ang-2 promotes neo-vascularization. Hence, angiopoietins exert crucial roles in the angiogenic switch during tumor progression, and increased expression of Ang-2 relative to Ang-1 in tumors correlates with poor prognosis. Its central role in the regulation of physiological and pathological angiogenesis makes the angiopoietin/Tie signaling pathway a therapeutically attractive target for the treatment of vascular disease and cancer.
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Authors | Ernesta Fagiani, Gerhard Christofori |
Journal | Cancer letters
(Cancer Lett)
Vol. 328
Issue 1
Pg. 18-26
(Jan 01 2013)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 22922303
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Copyright | Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Angiopoietins
- Receptor, TIE-1
- Receptor, TIE-2
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Topics |
- Angiopoietins
(metabolism)
- Humans
- Neoplasms
(blood supply)
- Neovascularization, Pathologic
- Receptor, TIE-1
(metabolism)
- Receptor, TIE-2
(metabolism)
- Signal Transduction
(physiology)
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