title: Mechanisms of pericyte recruitment in tumour angiogenesis: a new role for metalloproteinases.
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-beta1 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; (5) propagation of angiogenic signalling as cofactor; and (6) recruitment of bone marrow-derived stem cells.
authors.affiliation: Department of Paediatrics, Division of Haematology-Oncology, School of Medicine, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Christophe F
authors.initials: CF
authors.lastname: Chantrain
authors.forename: Patrick
authors.initials: P
authors.lastname: Henriet
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
authors.forename: Hervé
authors.initials: H
authors.lastname: Emonard
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Courtoy
authors.forename: Yves A
authors.initials: YA
authors.lastname: DeClerck
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
mesh_terms: D042683:Angiopoietin-1 / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000502:physiology*; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D020286:Pericytes / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1
chemical_list: D042683:Angiopoietin-1; D008246:Lysophospholipids; D020574:Proto-Oncogene Proteins c-sis; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C060506:sphingosine 1-phosphate; D020782:Matrix Metalloproteinases; D013110:Sphingosine