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 (GM3, GD3, GD1a, and GT1b synthases),
N-acetylgalactosaminyltransferases (GM2 and GD2 synthases), and
galactosyltransferase (GM1 and GD1b synthases) were analyzed in crude membrane preparations from these cells. The results confirmed the importance of GM3 and GD3 synthases in determining the prominence of the a (GM3 to GT1a) or b (GD3 to GQ1b) 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
GD2 ganglioside, the level of the preceding
enzyme in the pathway (GD3 synthase) was unexpectedly low. Thus, the high GD2:GD3 ratios characteristic of most
neuroblastomas result from low levels of GD3 synthase as well as high levels of
GD2 synthase. In other cell lines, GD3 synthase was completely absent, resulting in the synthesis of GM2, but not GD2, 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.