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

Overview

Journal Jpn J Cancer Res

Specialty Oncology

Date 1998 Apr 21

PMID 9548444

Citations 5

Authors

R Sawada

H Hotta

Y S Chung

M Sowa

T Tai

I Yano

Affiliations

Soon will be listed here.

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 (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.

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References

Yashiro M, Chung Y, Kubo T, Hato F, Sowa M . Differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts. Br J Cancer. 1996; 74(7):1096-103. PMC: 2077126. DOI: 10.1038/bjc.1996.496. View

Kleinman H, Martin G, Fishman P . Ganglioside inhibition of fibronectin-mediated cell adhesion to collagen. Proc Natl Acad Sci U S A. 1979; 76(7):3367-71. PMC: 383826. DOI: 10.1073/pnas.76.7.3367. View

Dohi T, Ohta S, Hanai N, Yamaguchi K, Oshima M . Sialylpentaosylceramide detected with anti-GM2 monoclonal antibody. Structural characterization and complementary expression with GM2 in gastric cancer and normal gastric mucosa. J Biol Chem. 1990; 265(14):7880-5. View

Gahmberg C, Hakomori S . Surface carbohydrates of hamster fibroblasts. I. Chemical characterization of surface-labeled glycosphingolipids and aspecific ceramide tetrasaccharide for transformants. J Biol Chem. 1975; 250(7):2438-46. View

Choi B, Yamaki T, Ibayashi Y, Maeda Y, Gasa S, Hashi K . Interleukin 4 enhances ganglioside GD3 expression on the human fibroblast cell line WI-38. J Biochem. 1995; 117(2):315-20. DOI: 10.1093/jb/117.2.315. View

Cheresh D, Pierschbacher M, Herzig M, Mujoo K . Disialogangliosides GD2 and GD3 are involved in the attachment of human melanoma and neuroblastoma cells to extracellular matrix proteins. J Cell Biol. 1986; 102(3):688-96. PMC: 2114134. DOI: 10.1083/jcb.102.3.688. View

Kannagi R, Levery S, Ishigami F, Hakomori S, Shevinsky L, Knowles B . New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen, stage-specific embryonic antigen 3. J Biol Chem. 1983; 258(14):8934-42. View

Yashiro M, Chung Y, Sowa M . Role of orthotopic fibroblasts in the development of scirrhous gastric carcinoma. Jpn J Cancer Res. 1994; 85(9):883-6. PMC: 5919589. DOI: 10.1111/j.1349-7006.1994.tb02963.x. View

Hakomori S . Cell density-dependent changes of glycolipid concentrations in fibroblasts, and loss of this response in virus-transformed cells. Proc Natl Acad Sci U S A. 1970; 67(4):1741-7. PMC: 283421. DOI: 10.1073/pnas.67.4.1741. View

10.

Iwamori M, Sakayori M, Nozawa S, Yamamoto T, Yago M, Noguchi M . Monoclonal antibody-defined antigen of human uterine endometrial carcinomas is Leb. J Biochem. 1989; 105(5):718-22. DOI: 10.1093/oxfordjournals.jbchem.a122734. View

11.

Laine R, Hakomori S . Incorporation of exogenous glycosphingolipids in plasma membranes of cultured hamster cells and concurrent change of growth behavior. Biochem Biophys Res Commun. 1973; 54(3):1039-45. DOI: 10.1016/0006-291x(73)90798-5. View

12.

Mannori G, Cecconi O, Mugnai G, Ruggieri S . Role of glycolipids in the metastatic process: characteristics of neutral glycolipids in clones with different metastatic potentials isolated from a murine fibrosarcoma cell line. Int J Cancer. 1990; 45(5):984-8. DOI: 10.1002/ijc.2910450535. View

13.

Wang S, Huang T, Hakomori S . Immunohistochemistry of two glycolipid tissue antigens in human gastric carcinoma. Cancer. 1983; 52(11):2072-6. DOI: 10.1002/1097-0142(19831201)52:11<2072::aid-cncr2820521117>3.0.co;2-x. View

14.

Okuno M, Chung Y, Sogabe T, Sowa M, Hotta H, Yano I . Le(b), a novel glycosphingolipid antigen of human distal colorectal cancer. Oncol Rep. 2011; 3(5):857-62. DOI: 10.3892/or.3.5.857. View

15.

Keranen A . Gangliosides of the human gastrointestinal mucosa. Biochim Biophys Acta. 1975; 409(3):320-8. DOI: 10.1016/0005-2760(75)90028-4. View

16.

Yashiro M, Chung Y, Nishimura S, Inoue T, Sowa M . Fibrosis in the peritoneum induced by scirrhous gastric cancer cells may act as "soil" for peritoneal dissemination. Cancer. 1996; 77(8 Suppl):1668-75. DOI: 10.1002/(SICI)1097-0142(19960415)77:8<1668::AID-CNCR37>3.0.CO;2-W. View

17.

Svennerholm L . CHROMATOGRAPHIC SEPARATION OF HUMAN BRAIN GANGLIOSIDES. J Neurochem. 1963; 10:613-23. DOI: 10.1111/j.1471-4159.1963.tb08933.x. View

18.

Keranen A, Lempinen M, Puro K . Ganglioside pattern and neuraminic acid content of human gastric and colonic carcinoma. Clin Chim Acta. 1976; 70(1):103-12. DOI: 10.1016/0009-8981(76)90010-3. View

19.

Blaszczyk M, Pak K, Herlyn M, Sears H, Steplewski Z . Characterization of Lewis antigens in normal colon and gastrointestinal adenocarcinomas. Proc Natl Acad Sci U S A. 1985; 82(11):3552-6. PMC: 397823. DOI: 10.1073/pnas.82.11.3552. View

20.

Kniep B, Hunig T, Fitch F, Heuer J, Kolsch E, Muhlradt P . Neutral glycosphingolipids of murine myeloma cells and helper, cytolytic, and suppressor T lymphocytes. Biochemistry. 1983; 22(2):251-5. DOI: 10.1021/bi00271a003. View