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  • Title: Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain.
    Author: Redondo-Muñoz J, Ugarte-Berzal E, Terol MJ, Van den Steen PE, Hernández del Cerro M, Roderfeld M, Roeb E, Opdenakker G, García-Marco JA, García-Pardo A.
    Journal: Cancer Cell; 2010 Feb 17; 17(2):160-72. PubMed ID: 20159608.
    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.
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