期刊
CANCER LETTERS
卷 328, 期 1, 页码 18-26出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.08.018
关键词
Angiogenesis; Angiopoietins; Pericytes; Tie receptors; Tumorigenesis; VEGFA
类别
资金
- EU-FP6 framework Program LYMPHANGIOGENOMICS [LSHG-CT-2004-503573]
- EU-FP7 framework Program TUMIC [2008-201662]
- NCCR Molecular Oncology of the Swiss National Science Foundation
- Swiss Cancer League
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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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