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.