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Glycosylation Pathways in the Biosynthesis of Gangliosides in Melanoma and Neuroblastoma Cells: Relative Glycosyltransferase Levels Determine Ganglioside Patterns¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021

In order to elucidate some of the factors that determine the characteristic expression of gangliosides in malignant melanoma and neuroblastoma the levels of ganglioside synthases (glycosyltransferases) were determined in a panel of cell lines from those tumors that exhibited a wide range of ganglioside composition. Sialyltransferases (G_M3, G_D3, G_D1a, and G_T1b synthases), N-acetylgalactosaminyltransferases (G_M2 and G_D2 synthases), and galactosyltransferase (G_M1 and G_D1b synthases) were analyzed in crude membrane preparations from these cells. The results confirmed the importance of G_M3 and G_D3 synthases in determining the prominence of the a (G_M3 to G_T1a) or b (G_D3 to G_Q1b) biosynthetic pathways. The overall ganglioside composition in cells was found to be dependent on the relative levels of specific enzymes acting sequentially or in competing pathways. In general, the pattern and levels of transferases correlated with the actual ganglioside content of the cell line, although several important discrepancies were noted. For example, in cell lines containing high amounts of G_D2 ganglioside, the level of the preceding enzyme in the pathway (G_D3 synthase) was unexpectedly low. Thus, the high G_D2:G_D3 ratios characteristic of most neuroblastomas result from low levels of G_D3 synthase as well as high levels of G_D2 synthase. In other cell lines, G_D3 synthase was completely absent, resulting in the synthesis of G_M2, but not G_D2, by N-acetylgalactosaminyltransferase I, as would be expected. It was concluded that different glycosyltransferases play key roles in determining glycolipid expression in different cell types.

¹ Supported by grants from the National Cancer Institute (CA08478 and CA21445).

² To whom requests for reprints should be addressed, at Sloan-Kettering Institute, Section 6155, 1275 York Avenue, New York, NY 10021.

Received 4/30/92. Accepted 8/ 6/92.

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