Document Detail


Constitutive activation of metalloproteinase ADAM10 in mantle cell lymphoma promotes cell growth and activates the TNF{alpha}/NF{kappa}B pathway.
MedLine Citation:
PMID:  21441465     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
One of the main functions of ADAM10, a disintegrin and metalloproteinase, is to regulate the bioavailability of adhesion molecules and ligands to various cellular signaling receptors. Constitutive activation of ADAM10 has been implicated in the pathogenesis of several types of solid tumors. In this study, we found that mantle cell lymphoma (MCL) cell lines and all 12 patient samples examined expressed the active/mature form of ADAM10. In contrast, peripheral blood mononuclear cells from healthy donors (n=5) were negative. By immunohistochemistry, ADAM10 was readily detectable in 20 of 23 (87%) MCL tumors but absent in 5 reactive tonsils. Knockdown of ADAM10 using siRNA in MCL cells significantly induced growth inhibition and cell-cycle arrest, and these changes correlated with a downregulation of cyclin D1, upregulation of p21(waf1), and significant reductions in the TNFα production/transcriptional activity of NFκBp65. Addition of recombinant ADAM10 to MCL cells led to the opposite biological effects. Lastly, downregulation of ADAM10 using siRNA enhanced the growth-suppressing effects mediated by proteasome inhibitors MG132 and bortezomib. To conclude, constitutive activation of ADAM10 contributes to the growth of MCL. Inhibition of ADAM10 may be a useful strategy to enhance the response of MCL to other therapeutic agents.
Authors:
Hanan Armanious; Pascal Gelebart; Mona Anand; Andrew Belch; Raymond Lai
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-25
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Laboratory Medicine and Pathology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada;
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