Inhibition of endogenous ganglioside synthesis does not block neurite formation by retinoic acid-treated neuroblastoma cells

Gangliosides are believed to play a critical role in cellular differentiation. To test this concept, we determined the effect of inhibition of endogenous ganglioside synthesis upon neurite formation induced by retinoic acid in LAN-B human neuroblastoma cells. Ganglioside synthesis and content of LAN-B cells exposed for 6 days to 10 mu M D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) (an inhibitor of glucosylceramide synthase) were reduced by >90%. However, these ganglioside depleted cells were not blocked from forming neurites when exposed to 10 mu M retinoic acid. Even more extensive treatment of LAN-5 cells with 20 mu M D-PDMP (6 day pretreatment followed by 6 days together with 10 mu M retinoic acid) still did not block the retinoic acid induced neurite formation. An element of neuroblastoma tumor cell differentiation, neurite formation, is therefore dependent neither on an intact cellular ganglioside complement nor on new ganglioside synthesis.