Skip Navigation



Glycobiology Advance Access published online on December 8, 2007
Glycobiology, doi:10.1093/glycob/cwm133
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
18/2/195    most recent
cwm133v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Fortier, S.
Right arrow Articles by Annabi, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fortier, S.
Right arrow Articles by Annabi, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Tetra- and Hexavalent Mannosides Inhibit the Pro-Apoptotic, Anti-Proliferative and Cell Surface Clustering Effects of Concanavalin-A : Impact on MT1-MMP Functions in Marrow-Derived Mesenchymal Stromal Cells

Simon Fortier1,2,, Mohamed Touaibia3,¶, Simon Lord-Dufour1,2,, Jacques Galipeau4, René Roy2 and Borhane Annabi1,2,*

1 Laboratoire d’Oncologie Moléculaire, Centre BioMed
2 Equipe PharmaQÀM, Département de Chimie, Université du Québec à Montréal, Quebec, Canada
3 Département de Chimie, Université de Moncton, Moncton, New-Brunswick, Canada
4 Department of Medicine, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada

* Correspondence should be directed to : Borhane Annabi, Laboratoire d’Oncologie Moléculaire, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada, H3C 3P8; Phone : (514) 987-3000 ext 7610; Fax : (514) 987-0246; E-mail : annabi.borhane{at}uqam.ca

Received on October 2, 2007; accepted on November 30, 2007

Mesenchymal stromal cells (MSC) mobilization and recruitment by experimental vascularizing tumors involves membrane type 1-matrix metalloproteinase (MT1-MMP) functions. Given that the mannose-specific lectin Concanavalin-A (ConA) induces MT1-MMP expression and mimics biological lectins/carbohydrate interactions, we synthesized and tested the potential of 11 mannoside clusters to block ConA activities on MSC. We found that tetra- and hexavalent mannosides reversed ConA-mediated changes in MSC morphology and antagonized ConA-induced caspase-3 activity and proMMP-2 activation. Tetra- and hexavalent mannosides also inhibited ConA- but not the cytoskeleton disrupting agent Cytochalasin-D-induced MT1-MMP cell surface proteolytic processing mechanisms, and effects on cell cycle phase progression. The anti-proliferative and pro-apoptotic impact of ConA on the MT1-MMP/glucose-6-phosphate transporter signalling axis was also reversed by these mannosides. In conclusion, we designed and identified glycocluster constructions that efficiently interfered with carbohydrate-binding proteins (lectins) interaction with oligosaccharide moieties of glycoproteins at the cell surface of MSC. These glycoclusters may serve in carbohydrate-based anticancer strategies through their ability to specifically target MT1-MMP pleiotropic functions in cell survival, proliferation, and extracellular matrix degradation.

Key words: Mesenchymal stromal cells / Concanavalin-A / Mannosides / MT1-MMP / Cancer

These authors contributed equally to this work


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.