Glycosphingolipid biosynthesis was examined using [3H]-galactose as a precursor as rat L6 myoblasts fused to form multinucleated myotubes. Incorporation of label into neutral glycolipids decreased steadily as the population of myotubes increased, so that final biosynthesis was one-half that observed with myoblasts (p less than 0.02). Conversely, ganglioside biosynthesis doubled during myoblast confluency (p less than 0.02) and then decreased as myotubes formed. Qualitatively, L6 cells synthesized large amounts of ganglioside GM3 during all myogenic phases. The major neutral glycosphingolipid products were lactosylceramide and paragloboside (nLcOse4Cer). Few changes in TLC autoradiographic patterns were noted during differentiation, with the exception of a slight decrease in ganglioside GM1. The results indicate that the biosynthesis of glycosphingolipids is tightly regulated during myogenesis in vitro and suggest a role for membrane gangliosides in muscle cell differentiation.

The distribution of neutral, or asialosyl-, glycosphingolipids and gangliosides in a rhabdomyosarcoma of alveolar type have been studied. Histologically, this muscle tumor is composed primarily of two cell types: one with oval or round hyperchromatic nuclei and very little cytoplasm, and one a giant cell, with multiple, peripherally placed nuclei and weakly staining eosinophillic cytoplasm. In comparing glycolipids of the rhabdomyosarcoma with normal muscle from the same leg, the striking alteration in the tumor was a virtual disappearance of ganglioside GM2. There was also a slight increase in GM3 and a decrease in GD1a. The asialosyl derivative of GM2 (GalNac-Gal-Glc-Cer) was markedly increased in the tumor. A loss of glucosylceramide was also observed. The results are discussed in terms of glycolipid metabolic changes in muscle oncogenesis and their implications.