In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. LB-342-LB-342
Abstract:
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation in peripheral blood of CD5+ B lymphocytes, which ‘ progressively infiltrate lymphoid tissues. Several molecules, including matrix metalloproteinase-9 (MMP-9), are involved in these processes and could represent therapeutic targets. We previously showed that MMP-9 plays an essential role in B-CLL cell migration through basement membranes or endothelial cells (Redondo-Muñoz et al., Blood 108: 3143, 2006). We also recently demonstrated that alpha4beta1 integrin and a 190 kDa CD44v isoform are receptors for MMP-9 in B-CLL but not in normal B cells and that the MMP-9 hemopexin domain is essential for these interactions. Binding of MMP-9 to B-CLL cells inhibited cell migration and this required MMP-9 proteolytic activity (Redondo-Muñoz et al., Blood 112: 169, 2008). To further define the role of surface-bound MMP-9 in B-CLL we have employed several techniques including western blot, zymography, immunofluorescence, immunoprecipitation, siRNA transfection, cell adhesion/soluble binding assays, apoptosis, and cell migration assays. B-CLL cells cultured on pro- or mature MMP-9, proMMP-9 hemopexin domain or proMMP-9 catalytically-inactive mutant, showed decreased spontaneous apoptosis. This was due to induction of a survival pathway involving Lyn activation, STAT3 phosphorylation and Mcl-1 upregulation and did not require catalytic activity. This pathway was induced in all B-CLL cases and was active in B-CLL lymphoid tissues. Our results highlight the role of MMP-9 in B-CLL pathogenesis and indicate that MMP-9 hemopexin domain could constitute a therapeutic target in this malignancy. Supported by grants PI060400 and SAF2009-07035 from the Ministerio de Ciencia e Innovación and by the Fundación de Investigación Médica Mutua Madrileña. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-342.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-LB-342
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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