Review Mechanisms of pericyte recruitment in tumour angiogenesis: A new role for metalloproteinases Christophe F. Chantrain a,b , Patrick Henriet b , Sonata Jodele c , Herve ´ Emonard b , Olivier Feron d , Pierre J. Courtoy b , Yves A. DeClerck c, *, Etienne Marbaix a,e a Department of Paediatrics, Division of Haematology–Oncology, School of Medicine, Catholic University of Louvain, Brussels, Belgium b Cell Biology Unit, Christian de Duve Institute of Cellular Pathology, School of Medicine, Catholic University of Louvain, 75 Avenue Hippocrate, B-1200 Brussels, Belgium c Department of Paediatrics and Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California and The Saban Research Institute of Childrens Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027, USA d Unit of Pharmacology and Therapeutics, School of Medicine, Catholic Universityof Louvain, 53 Avenue E. Mounier, B-1200 Brussels, Belgium e Department of Pathology, School of Medicine, Catholic University of Louvain, Brussels, Belgium ARTICLE INFO Article history: Received 5 July 2005 Received in revised form 1 November 2005 Accepted 4 November 2005 Available online 10 January 2006 Keywords: Pericyte Metalloproteinase Tumour Angiogenesis PDGF HB-EGF S1P TGF-b1 Angiopoietin 1 Abbreviations: a-SMA, a-smooth muscle actin ALK, activin-like kinase Ang1, angiopoietin 1 AngII, angiotensin II bFGF, basic fibroblast growth factor EC, endothelial cell ABSTRACT 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-b1 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 promo- tion 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; (5) propagation of angiogenic signalling as cofactor; and (6) recruitment of bone marrow-derived stem cells. Ó 2005 Elsevier Ltd. All rights reserved. 0959-8049/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2005.11.010 * Corresponding author: Tel.: +1 323 669 2150; fax: +1 323 664 9455. E-mail address: declerck@usc.edu (Y.A. DeClerck). EUROPEAN JOURNAL OF CANCER 42 (2006) 310 – 318 available at www.sciencedirect.com journal homepage: www.ejconline.com