Globotriaosyl ceramide and globoside as major glycolipid components of fibroblasts in scirrhous gastric carcinoma tissues.

Scirrhous gastric cancer is characteristic in that cancer cells proliferate and invade with prominent fibrosis. To search for the expression of specific carbohydrate chains in scirrhous gastric cancer, we have examined the glycosphingolipid composition of scirrhous cancer tissues (n=10) in comparison with that of non-scirrhous cancer tissues (n=10) by means of two-dimensional thin layer chromatography, followed by fast atom bombardment mass spectrometry of the individual glycolipids and immunostaining analysis. The major neutral glycosphingolipids from scirrhous gastric cancer tissues were identified as ceramide monohexoside, ceramide dihexoside, globotriaosyl ceramide (Gb3) and globoside (Gb4), while the major acidic glycosphingolipids were II3 NeuAcalpha-LacCer, II3 NeuAcalpha2-LacCer and sulfatide. Relative concentrations of Gb3 and Gb4 in scirrhous gastric cancer tissues (Gb3 + Gb4 = 58%) were two times higher than those in non-scirrhous gastric cancer tissues (29%). Orthotopic fibroblasts cloned from scirrhous gastric cancer tissues showed similar high concentrations of Gb3 and Gb4 to scirrhous gastric cancer tissues. Furthermore, immunohistochemical study revealed that Gb3 and Gb4 were expressed intensely on the fibroblasts. On the other hand, analysis of glycosphingolipids in four scirrhous gastric cancer cell lines yielded the following results. i) The contents of Gb3 and Gb4 were low (6%), compared with orthotopic fibroblasts (62%). ii) Significant amounts of Le(a) (pentaglycosylceramide) and Le(b) (hexa- and heptaglycosylceramides), which could not be detected in scirrhous cancer tissues, were observed. The results show that the major neutral glycosphingolipids such as Gb3 and Gb4 of scirrhous gastric cancer tissues were derived from orthotopic fibroblasts and not from the cancer cells.