Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells.
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.
Bennaceur
Karim
K
Laboratory of Dermatological Research, University of Lyon-1 EA 41-69, Edouard Herriot Hospital, Lyon, France. karim.bennaceur@newcastle.ac.uk
Popa
Iuliana
I
Chapman
Jessica Alice
JA
Migdal
Camille
C
Péguet-Navarro
Josette
J
Touraine
Jean-Louis
JL
Portoukalian
Jacques
J
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
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