Volume 272, Number 2, Issue of January 10, 1997 pp. 1349-1354
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Inhibition of Endogenous Ganglioside Synthesis Does Not Block Neurite Formation by Retinoic Acid-treated Neuroblastoma Cells

(Received for publication, April 3, 1996, and in revised form, September 27, 1996)

From the Glycobiology Program, Center for Cancer and Transplantation Biology, Children's Research Institute, and Departments of Pediatrics and Biochemistry/Molecular Biology, George Washington University School of Medicine, Washington, D. C. 20010

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 µM 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 µM retinoic acid. Even more extensive treatment of LAN-5 cells with 20 µM D-PDMP (6 day pretreatment followed by 6 days together with 10 µM 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.

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