ORBi: Detry Benoît - Matrix metalloproteinase-2 governs lymphatic vessel formation as an interstitial collagenase.

Reference : Matrix metalloproteinase-2 governs lymphatic vessel formation as an interstitial collage...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/122143

Title :	Matrix metalloproteinase-2 governs lymphatic vessel formation as an interstitial collagenase.
Language :	English
Author, co-author :	Detry, Benoît [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
	Erpicum, Charlotte [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
	Paupert, Jenny [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
	Blacher, Silvia [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Maillard, Catherine [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Bruyère, Françoise [> >]
	Pendeville, Helene [> >]
	Remacle, T [> >]
	LAMBERT, Vincent [Centre Hospitalier Universitaire de Liège - CHU > > Ophtalmologie >]
	Balsat, Cédric [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Ormenese, Sandra [Université de Liège - ULg > > GIGA-Management : Pl-forme imagerie cell. et cytom. de flux >]
	Lamaye, F [> >]
	Janssens, E [> >]
	Moons, L [> >]
	CATALDO, Didier [Centre Hospitalier Universitaire de Liège - CHU > > Pneumologie-Allergologie >]
	Kridelka, Frédéric [Université de Liège - ULg > Département des sciences cliniques > Gynécologie et obstétrique >]
	Carmeliet, P [> >]
	Thiry, Marc [Université de Liège - ULg > Département des sciences de la vie > Biologie cellulaire >]
	Foidart, Jean-Michel [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
	Struman, Ingrid [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
	Noël, Agnès [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Publication date :	24-May-2012
Journal title :	Blood
Publisher :	American Society of Hematology
Volume :	119
Issue/season :	21
Pages :	5048-56
Audience :	International
ISSN :	0006-4971
e-ISSN :	1528-0020
City :	Washington
Country :	DC
Keywords :	[en] lymphangiogenesis ; lymphatic capillary ; matrix metalloproteinases ; extracellular matrix ; extracellular matrix
Abstract :	[en] Lymphatic dysfunctions are associated with several human diseases, including lymphedema and metastatic spread of cancer. Although it is well recognized that lymphatic capillaries attach directly to interstitial matrix mainly composed of fibrillar type I collagen, the interactions occurring between lymphatics and their surrounding matrix have been overlooked. In this study, we demonstrate how matrix metalloproteinase (MMP)–2 drives lymphatic morphogenesis through Mmp2-gene ablation in mice, mmp2 knockdown in zebrafish and in 3D-culture systems, and through MMP2 inhibition. In all models used in vivo (3 murine models and thoracic duct development in zebrafish) and in vitro (lymphatic ring and spheroid assays), MMP2 blockage or down-regulation leads to reduced lymphangiogenesis or altered vessel branching. Our data show that lymphatic endothelial cell (LEC) migration through collagen fibers is affected by physical matrix constraints (matrix composition, density and cross-linking). Transmission electron microscopy (TEM) and confocal reflection microscopy using DQ-collagen highlight the contribution of MMP2 to mesenchymal-like migration of LEC associated with collagen fiber remodeling. Our findings provide new mechanistic insight into how LEC negotiate an interstitial type I collagen barrier and reveal an unexpected MMP2-driven collagenolytic pathway for lymphatic vessel formation and morphogenesis.
Permalink :	http://hdl.handle.net/2268/122143
Framework Programme / European Project :	FP7 ; 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.

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