期刊
EUROPEAN JOURNAL OF CANCER
卷 42, 期 3, 页码 310-318出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2005.11.010
关键词
pericyte; metalloproteinase; tumour; angiogenesis; PDGF; HB-EGF; S1P; TGF-beta 1; angiopoietin 1
类别
资金
- NCI NIH HHS [CA 81403] Funding Source: Medline
Pericytes occur in tumour blood vessels and are critical for the development of a functional vascular network. Targeting tumour pericytes is a promising anti-angiogenic therapy but requires identifying the mechanisms of their recruitment in tumour and addressing whether these mechanisms can be selectively harnessed. Among the pathways involved in pericyte recruitment during embryonic development, the contribution of platelet-derived growth factor B and sphingosine 1-phosphate is confirmed in tumour angiogenesis. The effect of angiopoietin 1 depends on the tumour model. Transforming growth factor-beta 1 enhances tumour vascularization and microvessel maturation. Recent reports suggest a participation of matrix metalloproteinases (MMP) in tumour pericyte recruitment that is consistent with the effect of certain MMPs in the development of microvasculature in embryonic development and in in vitro models of vascular remodelling. Here, we discuss the possibility for MMPs to contribute to pericyte recruitment at six levels: (1) direct promotion of pericyte invasion by extracellular matrix degradation; (2) stimulation of pericyte proliferation and protection against apoptosis by modification of the ECM; (3) activation of pericytes through the release of growth factor bound to the ECM; (4) transactivation of angiogenic cell surface receptor; (S) propagation of angiogenic signalling as cofactor; and (6) recruitment of bone marrow-derived stem cells. (C) 2005 Elsevier Ltd. All rights reserved.
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