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Título: | Matrix Metalloproteinase-9 Promotes Chronic Lymphocytic Leukemia B Cell Survival through Its Hemopexin Domain |
Autor: | Redondo-Muñoz, Javier CSIC ORCID ; Ugarte-Berzal, Estefanía CSIC ORCID; Terol, María José; Steen, Philippe E. Van den; Hernández del Cerro, Mercedes CSIC; Roderfeld, Martin; Roeb, Elke; Opdenakker, Ghislain; García-Marco, José A.; García-Pardo, Angeles CSIC ORCID | Palabras clave: | B-CLL cells MMP-9 |
Fecha de publicación: | 17-feb-2010 | Editor: | Elsevier | Citación: | Cancer Cell 17(2): 160-172 (2010) | Resumen: | Matrix metalloproteinase-9 (MMP-9) is the major MMP produced by B-CLL cells and contributes to their tissue infiltration by degrading extracellular and membrane-anchored substrates. Here we describe a different function for MMP-9 in B-CLL, which involves the hemopexin domain rather than its catalytic function. Binding of soluble or immobilized (pro)MMP-9, a catalytically inactive proMMP-9 mutant, or the MMP-9 hemopexin domain to its docking receptors α4β1 integrin and CD44v, induces an intracellular signaling pathway that prevents B-CLL apoptosis. This pathway is induced in all B-CLL cases, is active in B-CLL lymphoid tissues, and consists of Lyn activation, STAT3 phosphorylation, and Mcl-1 upregulation. Our results establish that MMP/receptor binding induces intracellular survival signals and highlight the role of (pro)MMP-9 in B-CLL pathogenesis | Versión del editor: | 10.1182/blood-2007-08-107300 | URI: | http://hdl.handle.net/10261/21236 | DOI: | 10.1016/j.ccr.2009.12.044 | ISSN: | 1535-6108 |
Aparece en las colecciones: | (CIB) Artículos |
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