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Matrix Metalloproteinase-9 Promotes Chronic Lymphocytic Leukemia B Cell Survival through Its Hemopexin Domain

AuthorsRedondo-Muñoz, Javier ; Ugarte-Berzal, Estefanía ; Terol, María José; Steen, Philippe E. Van den; Hernández del Cerro, Mercedes ; Roderfeld, Martin; Roeb, Elke; Opdenakker, Ghislain; García-Marco, José A.; García-Pardo, Angeles
KeywordsB-CLL cells
Issue Date17-Feb-2010
CitationCancer Cell 17(2): 160-172 (2010)
AbstractMatrix 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
Publisher version (URL)10.1182/blood-2007-08-107300
Appears in Collections:(CIB) Artículos
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