VEGFs and receptors involved in angiogenesis versus lymphangiogenesis

被引:641
作者
Lohela, Marja
Bry, Maija
Tammela, Tuomas
Alitalo, Kari [1 ]
机构
[1] Univ Helsinki, Biomedicum Helsinki, Lab Mol Canc Biol, FIN-00014 Helsinki, Finland
关键词
ENDOTHELIAL-GROWTH-FACTOR; PROMOTES TUMOR-METASTASIS; LYMPH-NODE METASTASIS; NITRIC-OXIDE SYNTHASE; FACTOR-C; VASCULAR-PERMEABILITY; TRANSGENIC MICE; TYROSINE KINASE; CELL GROWTH; SIGNAL-TRANSDUCTION;
D O I
10.1016/j.ceb.2008.12.012
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Vascular endothelial growth factors and their endothelial tyrosine kinase receptors are central regulators of vasculogenesis, angiogenesis and lymphangiogenesis. VEGF signalling through VEGFR-2 is the major angiogenic pathway, and blockage of VEGF/VEGFR-2 signalling is the first anti-angiogenic strategy for cancer therapy. VEGFR-1 seems to act as a negative regulator of VEGF-mediated angiogenesis during development, and as a stimulator of pathological angiogenesis when activated by its specific ligands PIGF and VEGF-B. PIGF recruits angiogenic macrophages to tumours, and targeting PIGF could therefore be beneficial in cancer. For VEGF-B, with very limited angiogenic potential, a new role has been identified in regulating lipid metabolism in the heart. VEGF-C and VEGF-D induce lymphangiogenesis via VEGFR-3 and have also been shown to be lymphangiogenic in tumours, stimulating metastasis. Mouse models of lymphoedema have established VEGF-C as a promising agent for pro-lymphangiogenic therapy. In addition to lymphangiogenesis, VEGFR-3 has also been shown to be important for angiogenesis, acting together with VEGF/VEGFR-2 and DII4/Notch signalling to control angiogenic sprouting. Increasing knowledge of the mechanisms regulating (lymph)angiogenesis should enable the development of better agents to combat metastasis and the resistance of tumours towards anti-angiogenic treatment, and of pro-(lymph)angiogenic treatment methods for ischaemic diseases and lymphoedema.
引用
收藏
页码:154 / 165
页数:12
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