title: Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells.
abstract: 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 into 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.
authors.affiliation: Laboratory of Dermatological Research, University of Lyon-1 EA 41-69, Edouard Herriot Hospital, Lyon, France. karim.bennaceur@newcastle.ac.uk
authors.forename: Karim
authors.initials: K
authors.lastname: Bennaceur
authors.forename: Iuliana
authors.initials: I
authors.lastname: Popa
authors.forename: Jessica Alice
authors.initials: JA
authors.lastname: Chapman
authors.forename: Camille
authors.initials: C
authors.lastname: Migdal
authors.forename: Josette
authors.initials: J
authors.lastname: Péguet-Navarro
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Touraine
authors.forename: Jacques
authors.initials: J
authors.lastname: Portoukalian
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000096:biosynthesis; D002518:Ceramides / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation; D005679:G(M3) Ganglioside / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007790:Lactosylceramides / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology; D019139:Tumor Escape
chemical_list: D015703:Antigens, CD; D061945:Caspase Inhibitors; D002518:Ceramides; D015853:Cysteine Proteinase Inhibitors; D005679:G(M3) Ganglioside; D005732:Gangliosides; D007790:Lactosylceramides; D009842:Oligopeptides; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; C009744:CDw17 antigen; C026226:ganglioside, GD3; D020169:Caspases