Glycobiology Advance Access published online on February 24, 2009
Glycobiology, doi:10.1093/glycob/cwp015
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DIFFERENT MECHANISMS ARE INVOLVED IN APOPTOSIS INDUCED BY MELANOMA GANGLIOSIDES ON HUMAN MONOCYTE-DERIVED DENDRITIC CELLS
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University of Lyon-1 EA 41-69, Laboratory of Dermatological Research, Building R, Edouard Herriot Hospital, 69437 Lyon Cx 03, France
Department of Transplantation and Clinical Immunology, University of Lyon-1 and Edouard Herriot Hospital, Lyon, France
University of Manchester, Faculty of Life Sciences, United Kingdom, England
* Institute of Macromolecular Chemistry Petru Poni, Iasi, Romania
Corresponding author: Karim BENNACEUR, University of Lyon-1 EA 41-69, Laboratory of Dermatological Research, Building R, Edouard Herriot Hospital, 69437 Lyon Cx 03, France. E-mail: karim.bennaceur{at}newcastle.ac.uk Bennaceur.karim{at}yahoo.fr
Received on May 16, 2008; accepted on February 6, 2009
Tumor escape is linked to multiple mechanisms, notably the liberation, by tumor cells, of soluble factors that inhibit the function of dendritic cells (DC). We have shown that melanoma gangliosides impair DC differentiation and induce their apoptosis. The present study was aimed to give insight about the mechanisms involved. DC apoptosis was independent of the catabolism of gangliosides since lactosylceramide did not induce cell death. Apoptosis induced by GM3 and GD3 gangliosides was not blocked by inhibitors of de novo ceramide biosynthesis, whereas the acid sphingomyelinase inhibitor desipramine only prevented apoptosis induced by GM3. Furthermore, our results suggest that DC apoptosis was triggered via caspase activation, and it was ROS-dependent with GD3 ganglioside, suggesting that GM3 and GD3 induced apoptosis through different mechanisms.
Key words: Melanoma / gangliosides / dendritic cells / apoptosis / ceramides / acid sphingomyelinase