Author/Authors :
Redondo-Muٌoz، نويسنده , , Javier and Ugarte-Berzal، نويسنده , , Estefanيa and Terol، نويسنده , , Marيa José and Van den Steen، نويسنده , , Philippe E. and Hernلndez del Cerro، نويسنده , , Mercedes and Roderfeld، نويسنده , , Martin and Roeb، نويسنده , , Elke and Opdenakker، نويسنده , , Ghislain and Garcيa-Marco، نويسنده , , José A. and Garcيa-Pardo، نويسنده , , Angeles، نويسنده ,
Abstract :
Summary
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.
