Reference : Matrix metalloproteinase-2 governs lymphatic vessel formation as an interstitial collage...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/122143
Matrix metalloproteinase-2 governs lymphatic vessel formation as an interstitial collagenase.
English
Detry, Benoît* mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Erpicum, Charlotte* mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Paupert, Jenny* mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Blacher, Silvia mailto [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 mailto [Centre Hospitalier Universitaire de Liège - CHU > > Ophtalmologie >]
Balsat, Cédric mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Ormenese, Sandra mailto [Université de Liège - ULg > > GIGA-Management : Pl-forme imagerie cell. et cytom. de flux >]
Lamaye, F [> >]
Janssens, E [> >]
Moons, L [> >]
CATALDO, Didier mailto [Centre Hospitalier Universitaire de Liège - CHU > > Pneumologie-Allergologie >]
Kridelka, Frédéric mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie et obstétrique >]
Carmeliet, P [> >]
Thiry, Marc mailto [Université de Liège - ULg > Département des sciences de la vie > Biologie cellulaire >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
Struman, Ingrid mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
* These authors have contributed equally to this work.
24-May-2012
Blood
American Society of Hematology
119
21
5048-56
Yes
International
0006-4971
1528-0020
Washington
DC
[en] lymphangiogenesis ; lymphatic capillary ; matrix metalloproteinases ; extracellular matrix ; extracellular matrix
[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.
http://hdl.handle.net/2268/122143
FP7 ; 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.

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