Reference : Dentin Matrix Protein 1 induces membrane expression of VE-cadherin on endothelial cells ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/86583
Dentin Matrix Protein 1 induces membrane expression of VE-cadherin on endothelial cells and inhibits VEGF-induced angiogenesis by blocking VEGFR-2 phosphorylation.
English
Pirotte, Sophie[Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Lamour, Virginie[Université de Liège - ULg > > Centre facultaire de rech. en cancérologie expérimentale >]
Noël, Agnès[Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Mottet, Denis[Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Castronovo, Vincenzo[Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - GIGA-R : Labo de recherche sur les métastases >]
Bellahcene, Akeila[Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
[en] Dentin matrix protein 1 (DMP1) is a member of the Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) family, a group of proteins initially described as mineralized extracellular matrices components. More recently, SIBLINGs have been implicated in several key steps of cancer progression, including angiogenesis. Although pro-angiogenic activities have been demonstrated for two SIBLINGs, the role of DMP1 in angiogenesis has not been addressed yet. We demonstrated that this extracellular matrix protein induced the expression of VE-cadherin, a key regulator of intercellular junctions and contact inhibition of growth of endothelial cells that is also known to modulate VEGFR-2 activity, the major high affinity receptor for VEGF. DMP1 induced VE-cadherin and p27(Kip1) expression followed by cell cycle arrest in human umbilical vein endothelial cells (HUVEC) in a CD44-dependent manner. VEGF-induced proliferation, migration and tubulogenesis responses were specifically blocked upon DMP1 pre-treatment of HUVEC. Indeed, subsequently to VE-cadherin induction, DMP1 inhibited VEGFR-2 phosphorylation and Src-mediated signaling. However, DMP1 did not interfere with bFGF-induced angiogenesis. In vivo, DMP1 significantly reduced laser-induced choroidal neovascularization lesions and tumor-associated angiogenesis. These data enable us to put DMP1 on the angiogenic chessboard for the first time and to identify this protein as a new specific inhibitor of VEGF-induced angiogenesis.
FP7 ; 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.
[Université de Liège - ULg > > Centre facultaire de rech. en cancérologie expérimentale >]
