Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain - PubMed (original) (raw)
. 2010 Feb 17;17(2):160-72.
doi: 10.1016/j.ccr.2009.12.044.
Affiliations
- PMID: 20159608
- DOI: 10.1016/j.ccr.2009.12.044
Free article
Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain
Javier Redondo-Muñoz et al. Cancer Cell. 2010.
Free article
Abstract
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 alpha4beta1 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.
2010 Elsevier Inc. All rights reserved.
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