Angiopoietins in angiogenesis

被引:534
作者
Fagiani, Ernesta [1 ]
Christofori, Gerhard [1 ]
机构
[1] Univ Basel, Dept Biomed, Inst Biochem & Genet, Mattenstr 28, CH-4058 Basel, Switzerland
基金
瑞士国家科学基金会; 欧盟第七框架计划;
关键词
Angiogenesis; Angiopoietins; Pericytes; Tie receptors; Tumorigenesis; VEGFA; RECEPTOR TYROSINE KINASE; ENDOTHELIAL-CELL SURVIVAL; TIE-2 LIGAND ANGIOPOIETIN-2; TUMOR ANGIOGENESIS; SIGNAL-TRANSDUCTION; MESSENGER-RNA; VASCULAR MORPHOGENESIS; POSTNATAL ANGIOGENESIS; EXTRACELLULAR-MATRIX; DISEASE PROGRESSION;
D O I
10.1016/j.canlet.2012.08.018
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:18 / 26
页数:9
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