Title: Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain
Authors: Redondo-Muñoz, Javier ×
Ugarte Berzal, Estefania
Terol, María José
Van den Steen, Philippe
Hernández del Cerro, Mercedes
Roderfeld, Martin
Roeb, Elke
Opdenakker, Ghislain
García-Marco, José A
García-Pardo, Angeles #
Issue Date: Feb-2010
Series Title: Cancer cell vol:17 issue:2 pages:160-172
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.
ISSN: 1535-6108
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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