| Abstract: |
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, GDla, and GTIb synthases), N-acetylgalactosaminyltransferases (GM2 and GD2 synthases), and galactosyltransferase (GMi and Gmb 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 GTi”) or b (GD3 to GQib) 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-acetylgalactosami-nyltransferase I, as would be expected. It was concluded that different glycosyltransferases play key roles in determining glycolipid expression in different cell types. © 1992, American Association for Cancer Research. All rights reserved. |
