Reference : Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor
Scientific journals : Article
Human health sciences : Hematology
http://hdl.handle.net/2268/4709
Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor
English
Stabile, Helena [University of Brescia > Department of Biomedical Sciences and Biotechnology > Unit of General Pathology and Immunology]
Mitola, Stefania [University of Brescia > Department of Biomedical Sciences and Biotechnology > Unit of General Pathology and Immunology]
Moroni, Emanuela [University of Brescia > Department of Biomedical Sciences and Biotechnology > Unit of General Pathology and Immunology]
Belleri, Mirella [University of Brescia > Department of Biomedical Sciences and Biotechnology > Unit of General Pathology and Immunology]
Nicoli, Stefania [University of Brescia > Department of Biomedical Sciences and Biotechnology > Unit of General Pathology and Immunology]
Coltrini, Daniela [University of Brescia > Department of Biomedical Sciences and Biotechnology > Unit of Histology]
Peri, Francesco [University of Milan-Bicocca > Department of Biotechnology and Biosciences]
Pessi, Antonello [Istituto di Ricerche di Biologia Molecolare P. Angeletti (Rome)]
Orsatti, Laura [Istituto di Ricerche di Biologia Molecolare P. Angeletti (Rome)]
Talamo, Fabio [Istituto di Ricerche di Biologia Molecolare P. Angeletti (Rome)]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Waltregny, David mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases >]
Cotelli, Franco [University of Milan > Department of Biology]
Ribatti, Domenico [University of Bari > Department of Human Anatomy and Histology]
Presta, Marco [University of Brescia > Department of Biomedical Sciences and Biotechnology > Unit of General Pathology and Immunology]
1-Mar-2007
Blood
Amer Soc Hematology
109
5
1834-1840
Yes (verified by ORBi)
International
0006-4971
Washington
[en] Angiogenesis plays a key role in various physiologic and pathologic conditions, including tumor growth. Drm/gremlin, a member the Dan family of bone morphogenic protein (BMP) antagonists, is commonly thought to affect different processes during growth, differentiation, and development by heterodimerizing various BMPs. Here, we identify Drm/gremlin as a novel proangiogenic factor expressed by endothelium. Indeed, Drm/gremlin was purified to homogeneity from the conditioned medium of transformed endothelial cells using an endothelial-cell sprouting assay to follow protein isolation. Accordingly, recombinant Drm/gremlin stimulates endothelial-cell migration and invasion in fibrin and collagen gels, binds with high affinity to various endothelial cell types, and triggers tyrosine phosphorylation of intracellular signaling proteins. Also, Drm/gremlin induces neovascularization in the chick embryo chorioallantoic membrane. BMP4 does not affect Drm/gremlin interaction with endothelium, and both molecules exert a proangiogenic activity in vitro and in vivo when administered alone or in combination. Finally, Drm/gremlin is produced by the stroma of human tumor xenografts in nude mice, and it is highly expressed in endothelial cells of human lung tumor vasculature when compared with nonneoplastic lung. Our observations point to a novel, previously unrecognized capacity of Drm/gremlin to interact directly with target endothelial cells and to modulate angiogenesis.
http://hdl.handle.net/2268/4709

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