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-5 human neuroblastoma cells. Ganglioside synthesis and content of LAN-5 cells exposed for 6 days to 10 microM 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 microM retinoic acid. Even more extensive treatment of LAN-5 cells with 20 microM D-PDMP (6 day pretreatment followed by 6 days together with 10 microM 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.
Li
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R
Center for Cancer and Transplantation Biology, Children's Research Institute, Washington, D.C. 20010, USA.
Ladisch
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S
D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005732:Gangliosides / Q000096:biosynthesis*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D016501:Neurites / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D005732:Gangliosides; D009025:Morpholines; D014212:Tretinoin; C033110:RV 538; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase