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Ganglioside distribution in murine neural tumors

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Molecular and Chemical Neuropathology

Abstract

The ganglioside composition of seven experimental brain tumors was examined in C57BL/6J mice. The tumors were produced from 20-methylcholanthrene (20-MC) implantation into either the cerebrum or cerebellum and were maintained in serial transplants through many generations. The tumors studied were grown subcutaneously as solid tumors, and cells from two of the tumors were also studied in culture. Histologically, all of the tumors were similar and could be broadly classified as highly malignant, poorly differentiated anaplastic astrocytomas. The total ganglioside sialic acid content of the solid tumors was markedly lower than that in adult mouse brain. In addition toN-acetylneuraminic acid (NeuAc), the gangliosides in the solid tumors contained significant amounts ofN-glycolylneuraminic acid (NeuGc). The seven solid tumors fell into two general groups with respect to ganglioside composition. Furthermore, the differences in ganglioside composition between the two tumor groups were strongly associated with differences in tumor cell cohesion. The tumors in one group had high levels of GM3 hematosides, low levels of oligosialogangliosides, and grew as firm cohesive tissues. The tumors in the other group, however, had lower levels of GM3 hematosides, noticeable amounts of oligosialogangliosides and grew as soft noncohesive tissues. In culture, clonal cells from one of the tumors in the first group grew as clumps or islands and contained GM3 as the only major ganglioside, whereas clonal cells from a tumor in the second group grew as sheets or monolayers and contained little GM3, but expressed several gangliosides with complex structures. In marked contrast to the gangliosides in the solid tumors, the gangliosides in the cultured tumor cells contained trace amounts of NeuGc. Since NeuGc containing gangliosides are abundant in mouse nonneural tissues, the high content of NeuGc gangliosides in the solid tumors may arise from infiltration of nonneural tissue elements, e.g., macrophages, lymphocytes, and endothelial cells.

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Abbreviations

NeuAc:

N-acetylneuraminic acid

NeuGc:

N-glycolylneuraminic acid

References

  • Ando S. and Yu R. K. (1977) Isolation and characterization of a novel trisialoganglioside, GT1a, from human brain.J. Biol. Chem. 252, 6247–6250.

    PubMed  CAS  Google Scholar 

  • Ando S., Chang N. C., and Yu R. K. (1978) High performance thin layer chromatography and densitometric determination of brain ganglioside compositions of several species.Anal. Biochem. 89, 427–450.

    Article  Google Scholar 

  • Ando S. and Yu R. K. (1979) Isolation and characterization of two isomers of brain tetrasialogangliosides.J. Biol. Chem. 254, 12224–12229.

    PubMed  CAS  Google Scholar 

  • Aruna R. M. and Basu D. (1975). Glycolipid metabolism in tumours of central nervous system.Ind. J. Biochem. Biophys. 13, 158–160.

    Google Scholar 

  • Asou H. and Brunngraber E. G. (1983) Absence of ganglioside GM1 in astroglial cells from 21-day old rat brain.Neurochem. Res. 8, 1045–1057.

    Article  PubMed  CAS  Google Scholar 

  • Berra B., Riboni L., De Gasperi R., Gaini S. M., and Ragnotti G. (1983) Modifications of ganglioside patterns in human meningiomas.J. Neurochem. 40, 777–782.

    Article  PubMed  CAS  Google Scholar 

  • Berra B., Gaini S. M., and Riboni L. (1985) Correlation between ganglioside distribution and histological grading of human astrocytomas.Int. J. Cancer 36, 363–366.

    PubMed  CAS  Google Scholar 

  • Cheresh D. A., Pierschbacher M. D., Herzig M. A., and Kalplana M. (1986) Disialogangliosides GD2 and GD3 are involved in the attachment of human melanoma and neuroblastoma cells to extracellular matrix proteins.J. Cell Biol. 102, 688–696.

    Article  PubMed  CAS  Google Scholar 

  • Chou K. H., Ambers S. A., and Jungalwala F. B. (1979) Ganglioside composition of chemically induced rat neural tumors and characterization of hematoside from neurinomas.J. Neurochem. 33, 863–873.

    Article  PubMed  CAS  Google Scholar 

  • Crafts D. and Wilson C. B. (1977) Animal models of brain tumors.Natl. Cancer Inst. Monogr. 46, 11–17.

    PubMed  CAS  Google Scholar 

  • Dawson G., Kemp S. F., Stoolmiller A. C., and Dorfman A. (1971) Biosynthesis of glycosphingolipids by mouse neuroblastoma (NB41A), rat glia (RGC-6) and human glia (CHB-4) in cell culture.Biochem. Biophys. Res. Commun. 44, 687–694.

    Article  PubMed  CAS  Google Scholar 

  • Dawson G. and Stoolmiller A. C. (1976) Comparison of the ganglioside composition of established mouse neuroblastoma cell strains growingin vivo and in tissue culture.J. Neurochem. 26, 225–226.

    Article  PubMed  CAS  Google Scholar 

  • Dawson G. (1979) Regulation of glycosphingolipid metabolism in mouse neuroblastoma and glioma cell lines.J. Biol. Chem. 254, 155–162.

    PubMed  CAS  Google Scholar 

  • Dimpfel W. (1982) Differential distribution of gangliosides in nerve-cell cultures.Cell Molec. Neurobiol. 2, 105–113.

    Article  CAS  Google Scholar 

  • Dreyfus H., Louis J. C., Harth S., and Mandel, P. (1980) Gangliosides in cultured neurons.Neuroscience 5, 1647–1655.

    Article  PubMed  CAS  Google Scholar 

  • Duffard R. O., Fishman P. H., Bradley R. M., Lauter C. J., Brady R. O., and Trams E. G. (1977) Ganglioside composition and biosynthesis in cultured cells derived from CNS.J. Neurochem. 28, 1161–1166.

    Article  PubMed  CAS  Google Scholar 

  • Eto Y. and Shinoda S. (1982) Gangliosides and neutral glycolipids in human brain tumors: specificity and their significance.Adv. Exp. Med. Biol. 152, 279–290.

    PubMed  CAS  Google Scholar 

  • Flavin H. J., Wieraszko A., and Seyfried T. N. (1991) Enhanced aspartate release from hippocampal slices of epileptic (EI) mice.J. Neurochem. 56, 1007–1011.

    Article  PubMed  CAS  Google Scholar 

  • Fredman P. (1988) Gangliosides in human malignant gliomas, inNew Trends in Ganglioside Research: Neurochemical and Neurogenerative Aspects (Ledeen R. W., Hogan E. L., Tettamanti G., Yates A., and Yu R. K., eds.) pp. 151–161, Liviana, Padova.

    Google Scholar 

  • Fredman P., von Holst H., Collins V. P., Ammar A., Dellheden B., Wahren B. Granholm L., and Svennerholm L. (1986) Potential ganglioside antigens associated with human gliomas.Neurol. Res. 8, 123–126.

    PubMed  CAS  Google Scholar 

  • Fredman P., von Holst H., Collins P. V., Granholm L., and Svennerholm L. (1989) Sialosyllactotetraosylceramide, a ganglioside marker for human malignant gliomas.J. Neurochem. 50, 912–919.

    Article  Google Scholar 

  • Galloway P. G. and Roessmann U. (1986) Anaplastic astrocytoma mimicking metastatic carcinoma.Am. J. Surg. Pathol. 10, 728–732.

    Article  PubMed  CAS  Google Scholar 

  • Gaini S. M., Riboni L., Ceri C., Grimoldi N., Sganzerla E. P., and Berra B. (1988) Ganglioside content and composition in human gliomas.Acta Neurochirurg.43 (Suppl.), 126–129.

    CAS  Google Scholar 

  • Gottfries J., Fredman P., Mansson J. E., Collins P. V., von Holst H., Armstrong D. D., Percy A. K., Wikstrand C. J., Bigner D. D., and Svennerholm L. (1990) Determination of gangliosides in six human primary medulloblastomas.J. Neurochem. 55, 1322–1326.

    Article  PubMed  CAS  Google Scholar 

  • Hakomori S. I. and Kannagi R. (1983) Glycosphingolipids as tumor-associated and differentiated markers.J. Natl. Cancer Inst. 71, 231–251.

    PubMed  CAS  Google Scholar 

  • Hamanaka S., Handa S., and Yamakawa T. (1979) Ganglioside compositions of erythrocytes from various strains of inbred mice.J. Biochem. 86, 1623–1626.

    PubMed  CAS  Google Scholar 

  • Hirabayashi Y., Taki T., Matsumoto M., and Kojima K. (1977) Comparative study on glycolipid composition, between two cell types of rat ascites hepatoma cells.Biochim. Biophys. Acta 529, 96–105.

    Google Scholar 

  • Huang R. T. C. (1978) Cell adhesion mediated by glycolipids.Nature 276, 624–626.

    Article  PubMed  CAS  Google Scholar 

  • Iglesias J. R., Pfannkuch F., Aruffo C., Kazner E., and Navarro J. (1986) Histopathological diagnosis of brain tumors with the help of a computer: mathematical fundamentals and practical application.Acta Neuropathol. 71, 130–135.

    Article  PubMed  CAS  Google Scholar 

  • Jennemann R., Rodden A., Bauer B. L., Mennel H. D., and Wiegandt H. (1990) Glycosphingolipids of human gliomas.Cancer Res. 50, 7444–7449.

    PubMed  CAS  Google Scholar 

  • Kawai T., Kato A., Higashi H., Kato S. and Naiki M. (1991) Quantitative determination of N-glycolylneuraminic acid expression in human cancerous tissues and avain lymphoma cell lines as a tumor-associated sialic acid by gas chromatography-mass spectrometry.Cancer Res. 51, 1242–1246.

    PubMed  CAS  Google Scholar 

  • Kojima N. and Hakomori S.-I. (1989) Specific interaction between gangliotriaosylceramide (Gg3) and sialosyllactosylceramide (GM3) as a basis for specific cellular recognition between lymphoma and melanoma cells.J. Biol. Chem. 264, 20159–20162.

    PubMed  CAS  Google Scholar 

  • Kostic D. and Buchheit F. (1970) Gangliosides in human brain tumors.Life Sci. 9, 589–596.

    Article  CAS  Google Scholar 

  • Ladish S. (1989) Tumor gangliosides; Shedding, structural characterization and immunosuppressive activity, inGangliosides and Cancer (H. F. Oettgen, ed.) pp. 219–229, VCH, New York.

    Google Scholar 

  • Ledeen R. W., Yu R. K., and Eng L. F. (1973) Gangliosides of human myelin: sialosygalactosylceramide (G7) as a major component.J. Neurochem. 21, 829–839.

    Article  PubMed  CAS  Google Scholar 

  • Mandel P., Dreyfus H., Yusuf A. N. K., Sarlieve L., Robert J., Neskovic J, Harth S., and Rebel G. (1980) Neuronal and glial cell cultures, a tool for investigation of ganglioside function.Adv. Exp. Biol. Med. 125, 515–531.

    CAS  Google Scholar 

  • Mansson J. E., Fredman P., Bigner D. D., Molin K., Rosengren B., Friedman H. S., and Svennerholm L. (1986). Characterization of new gangliosides of the lactotetraose series in murine xenographs of a human glioma cell line.FEBS Lett. 201, 109–113.

    Article  PubMed  CAS  Google Scholar 

  • Manuelidis L., Yu R. K., and Manuelidis E. E. (1977) Ganglioside content and pattern in human gliomas in culture.Acta Neuropath. (Berl.)38, 129–135.

    Article  CAS  Google Scholar 

  • Miller-Podraza H., Bradley R., and Fishman P. (1982) Biosynthesis and localization of gangliosides.Biochemistry 21, 3260–3265.

    Article  PubMed  CAS  Google Scholar 

  • Nilsson O., Mansson J. E., Lindholm L., Holmgren J., and Svennerholm L. (1985) Sialosyllactotetraosylceramide, a novel ganglioside antigen detected in human carcinomas by a monoclonal antibody.FEBS Lett. 182, 398–402.

    Article  PubMed  CAS  Google Scholar 

  • Okada Y, Mugnai G., Bremer E. G., and Hakomori D. (1984) Glycosphingolipids in detergent-insoluble substrate attachment matrix (DISAM) prepared from substrate attachment material (SAM).Exp. Cell Res. 155, 448–456.

    Article  PubMed  CAS  Google Scholar 

  • Reynolds B. A. and Weiss S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.Science 255, 1707–1710.

    Article  PubMed  CAS  Google Scholar 

  • Robert J., Freysz L., Sensenbrenner M., Mandel P., and Rebel G. (1975) Gangliosides of glial cells: A comparative study of normal astroblasts in tissue culture and glial cells isolated on sucrose-ficoll gradients.FEBS Lett. 50, 144–146.

    Article  PubMed  CAS  Google Scholar 

  • Robert J., Rebel G., and Mandel P. (1977) Glycosphingolipids from cultured astroblasts.J. Lipid Res. 18, 517–522.

    PubMed  CAS  Google Scholar 

  • Roessmann U., Velasco M. E., Gambetti P., and Autilio-Gambetti L. (1983) Neuronal and astrocytic differentiation in human neuroepithelial neoplasms.J. Neuropathol. Exp. Neurol. 42, 113–121.

    Article  PubMed  CAS  Google Scholar 

  • Rorke L. B. (1983) The cerebellar medulloblastoma and its relationship to primitive neuroectodermal tumors.J. Neuropathol. Exp. Neurol. 42, 1–15.

    Article  PubMed  CAS  Google Scholar 

  • Roseman S. (1970) The synthesis of complex carbohydrates by multiglycosyl-transferase systems and their potential function in intracellular adhesion.Chem. Phys. Lipids 5, 270–297.

    Article  PubMed  CAS  Google Scholar 

  • Rubin R., Sutton C. H., and Zimmerman H. M. (1968) Experimental ependymoblastoma (fine structure).J. Neuropathol. Exp. Neurol. 27, 421–438.

    Article  Google Scholar 

  • Rubinstein L. J. (1977) Correlation of animal brain tumor models with human neuro-oncology.Natl. Cancer Inst., Monogr. 46, 43–49.

    CAS  Google Scholar 

  • Rutishauser U., Acheson A., Hall A. K., Mann D. M., and Sunshine J. (1988) The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions.Science 240, 53–57.

    Article  PubMed  CAS  Google Scholar 

  • Sbaschnig-Agler M., Dreyfus H., Norton W. T., Sensenbrenner M., Farooq M., Byrne M., and Ledeen R. W. (1988) Gangliosides of cultured astroglia.Brain Res. 461, 98–106.

    Article  PubMed  CAS  Google Scholar 

  • Schauer R. (1985) Sialic acids and their roles as biological masks.Trends Biochem. Sci. 10, 357–360.

    Article  CAS  Google Scholar 

  • Schengrund C. L. and Nelson J. T. (1976) Sialidase activity in mouse neuroblastoma cell lines.Neurochem. Res. 1, 181–190.

    Article  Google Scholar 

  • Schengrund C. L., Repman M. A., and Shochat S. J. (1985) Ganglioside composition of human neuroblastomas.Cancer 56, 2640–2646.

    Article  PubMed  CAS  Google Scholar 

  • Schold S. C. and Bigner D. D. (1983) A review of animal brain tumor models that have been used for therapeutic studies, inOncology of the Nervous System (Walker M. D., ed.) pp. 31–64, Martinus Nijhoff, Boston.

    Google Scholar 

  • Schulz G., Cheresh D. A., Varki N. M., Yu A., Staffileno L. K., and Reisfeld R. A. (1984) Detection of ganglioside GD2 in tumor tissue and sera of neuroblastoma patients.Cancer Res. 44, 5914–5920.

    PubMed  CAS  Google Scholar 

  • Schwarting G. A. and Gajewski A. (1983) Glycolipids of murine lymphocyte subpopulations.J. Biol. Chem. 258, 5693–5698.

    Google Scholar 

  • Seyfried T. N., Ando S., and Yu R. K. (1978a) Isolation and characterization of human liver hematoside.J. Lipid Res. 19, 538–543.

    PubMed  CAS  Google Scholar 

  • Seyfried T. N., Glaser G. H., and Yu R. K. (1978b) Cerebral, cerebellar, and brain stem gangliosides in mice susceptible to audiogenic seizures.J. Neurochem. 31, 21–27.

    Article  PubMed  CAS  Google Scholar 

  • Seyfried T. N., Itoh T., Miyazawa N., and Yu R. K. (1981) Cerebellar gangliosides and phosopholipids in mutant mice with ataxia and epilepsy: The tottering/leaner syndrome.Brain Res. 216, 429–436.

    Article  PubMed  CAS  Google Scholar 

  • Seyfried T. N., Yu R. K., Saito M., and Albert M. (1987) Ganglioside composition of an experimental mouse brain tumor.Cancer Res. 47, 3538–3542.

    PubMed  CAS  Google Scholar 

  • Seyfried T. N., Roy M. L., and El-Abbadi M. (1991) Ganglioside composition of neural tumors in mice.Trans. Am. Soc. Neurochem. 22, 269.

    Google Scholar 

  • Shochat S. J., Corbelleta N. L., Repman M. A., and Schengrund C. L. (1987) A biochemical analysis of thoracic neuroblastomas: A pediatric oncology group of study.J. Ped. Surg. 22, 660–664.

    Article  CAS  Google Scholar 

  • Stoolmiller A. C., Dawson G., Kemp S. F., and Schachner M. (1979) Synthesis of glycosphingolipids in mouse glial tumors.J. Neurochem. 32, 637–641.

    Article  PubMed  CAS  Google Scholar 

  • Traylor T. D. and Hogan E. L. (1980) Gangliosides of human astrocytomas.J. Neurochem. 34, 126–131.

    Article  PubMed  CAS  Google Scholar 

  • Tsuchida T., Ravindranath M. H., Saxton R. E. and Irie R. (1987) Gangliosides of human melanoma: Altered expressionin vivo andin vitro.Cancer Res. 47, 1278–1281.

    PubMed  CAS  Google Scholar 

  • Ueno K., Ando S., and Yu R. K. (1978) Gangliosides of human, cat and rabbit spinal cords and cord myelin.J. Lipid Res. 19, 863–871.

    PubMed  CAS  Google Scholar 

  • Van Echten G. and Sandhoff K. (1989) Modulation of ganglioside biosynthesis in primary cultured neurons.J. Neurochem. 52, 207–214.

    Article  PubMed  Google Scholar 

  • Wu Z. L., Schwartz E., Seeger R., and Ladisch S. (1986) Expression of GD2 by untreated primary human neuroblastomas.Cancer Res. 46, 440–443.

    PubMed  CAS  Google Scholar 

  • Yamasaki T., Handa H., Yamashita J., Watanabe Y., Namba Y., and Hanaoka M. (1984) Specific adoptive immunotherapy with tumor-specific cytotoxic T-lymphocyte clone for murine malignant gliomas.Cancer Res. 44, 1776–1783.

    PubMed  CAS  Google Scholar 

  • Yates A. J. (1988) Glycolipids and gliomas: A review.Neurochem. Pathol. 8, 157–179.

    PubMed  CAS  Google Scholar 

  • Yates A. J., Thompson D. K., Boesel C. P., Albrightson C., and Hart R. W. (1979) Lipid composition of human neural tumors.J. Lipid Res. 20, 428–436.

    PubMed  CAS  Google Scholar 

  • Yogeeswaran G., Wherrett J. R., Chatterjee S., and Murry, R. K. (1970) Ganglioside of cultured mouse cells: Partial characterization and demonstration of14C-glucosamine incorporation.J. Biol. Chem. 245, 6718–6725.

    PubMed  CAS  Google Scholar 

  • Yogeeswaran G., Murry R. K., Pearson M. L., Sanwal B. D., McMorris F. A., and Ruddle F. H. (1973) Glycospingolipids of clonal lines of mouse neuroblastoma and neuroblastoma XL cell hybrids.J. Biol. Chem. 248, 1231–1239.

    PubMed  CAS  Google Scholar 

  • Yohe H. C., Coleman D. L., and Ryan J. (1985) Ganglioside alteration in stimulated murine macrophages.Biochem. Biophys. Acta 818, 81–86.

    Article  PubMed  CAS  Google Scholar 

  • Yohe H. C. and Ryan J. L. (1986) Ganglioside expression in macrophages from endotoxin responder and nonendotoxin responder mice.J. Immunol. 127, 3921–3927.

    Google Scholar 

  • Yu R. K., and Ledeen R. W. (1970) Gas-liquid chromatographic assay of lipid-bound sialic acids: Measurement of gangliosides in brains of several species.J. Lipid Res. 11, 506–516.

    PubMed  CAS  Google Scholar 

  • Zimmerman H. M. and Arnold H. (1941) Experimental brain tumors: I. Tumors produced with methylcholanthrene.Cancer Res. 1, 919–938.

    CAS  Google Scholar 

  • Zulch K. J. (1980) Principles of the new World Health Organization (WHO) classification of brain tumors.Neuroradiology 19, 59–66.

    Article  PubMed  CAS  Google Scholar 

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Seyfried, T.N., El-Abbadi, M. & Roy, M.L. Ganglioside distribution in murine neural tumors. Molecular and Chemical Neuropathology 17, 147–167 (1992). https://doi.org/10.1007/BF03159989

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