Globotriaosyl Ceramide and Globoside as Major Glycolipid Components of Fibroblasts in Scirrhous Gastric Carcinoma Tissues

Abstract

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 (Gb 3 ) and globoside (Gb 4 ), while the major acidic glycosphingolipids were II 3 NeuAcα α α α-LacCer, II 3 NeuAcα α α α 2 -LacCer and sulfatide. Relative concentrations of Gb 3 and Gb 4 in scirrhous gastric cancer tissues (Gb 3 + + + + Gb 4 = = = =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 Gb 3 and Gb 4 to scirrhous gastric cancer tissues. Furthermore, immunohistochemical study revealed that Gb 3 and Gb 4 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 Gb 3 and Gb 4 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 Gb 3 and Gb 4 of scirrhous gastric cancer tissues were derived from orthotopic fibroblasts and not from the cancer cells.Key words: Glycosphingolipid -Scirrhous gastric cancer -Fibroblast -Globotriaosyl ceramideGlobosideScirrhous gastric cancer has a characteristic histological progression with prominent proliferation of interstitial tissues, and the diagnosis is so difficult at early stages that the prognosis is poor, compared with that of non-scirrhous-type gastric cancer.3) One of reason for the difficulty of diagnosis at early stages is the small change of the mucosal lesion. When scirrhous gastric cancer cells invade the submucosa, the cancer cells proliferate diffusely with prominent fibrosis. The mechanism responsible for such characteristic biological behavior is not well understood. Recently, the existence of a specific interaction between scirrhous gastric cancer cells and orthotopic fibroblasts has been reported. i) Gastric orthotopic fibroblasts specifically stimulated the growth of scirrhous gastric cancer cells, but not that of well-differentiated gastric cancer cells. 4,5) ii) Scirrhous gastric cancer cells significantly stimulated the growth of peritoneal fibroblasts, but well differentiated adenocarcinoma cells did not. 6) In an attempt to identify possible cell-to-cell interacti...

Lipidomic Analysis of Archival Pathology Specimens Identifies Altered Lipid Signatures in Ovarian Clear Cell Carcinoma

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Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit

“…There are only few reports on Gb 3 expression in stomach cancer. However, it was previously shown that stroma fibroblasts in scirrhous carcinomas, a rare subgroup of diffuse-type cancer featuring important stromal components, express Gb 3 (44).…”

Glycosphingolipids with Very Long-Chain Fatty Acids Accumulate in Fibroblasts from Adrenoleukodystrophy Patients

“…We identified 23 species of HexCer and 15 species of LacCer, which are more than those previously reported by other groups [30,31]. Matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis of cultured skin fibroblasts identified six species of HexCer [30]. Scherer et al found four species of HexCer and LacCer (Hex 2 Cer) in primary human skin fibroblasts by hydrophilic interaction liquid chromatography-tandem mass spectrometry [31].…”

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