Expression of Mouse Sialic Acid on Gangliosides of a Human Glioma Grown as a Xenograft in SCID Mice

Authors

  • Jeffrey A. Ecsedy,

    1. Department of Biology, Boston College, Chestnut Hill, Massachusetts, U.S.A.*VA Medical and Regional Office Center, White River Junction, Vermont, U.S.A.Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • Kathryn A. Holthaus,

    1. Department of Biology, Boston College, Chestnut Hill, Massachusetts, U.S.A.*VA Medical and Regional Office Center, White River Junction, Vermont, U.S.A.Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • Herbert C. Yohe,

    1. Department of Biology, Boston College, Chestnut Hill, Massachusetts, U.S.A.*VA Medical and Regional Office Center, White River Junction, Vermont, U.S.A.Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • Thomas N. Seyfried

    1. Department of Biology, Boston College, Chestnut Hill, Massachusetts, U.S.A.*VA Medical and Regional Office Center, White River Junction, Vermont, U.S.A.Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.
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  • Lippincott Williams & Wilkins, Inc., Philadelphia

  • Abbreviations used: GalCer, galactosylceramide; GlcCer, glucosylceramide; GSL, glycosphingolipid; HPTLC, high-performance thinlayer chromatography; LacCer, lactosylceramide; NeuAc, N-acetylneuraminic acid; NeuGc, N-glycolylneuraminic acid; NGSL, neutral glycosphingolipid; SCID, severe combined immunodeficiency.

Address correspondence and reprint requests to Dr. T. N. Seyfried at Department of Biology, Boston College, Chestnut Hill, MA 02467-3811, U.S.A.

Abstract

Abstract: Ganglioside sialic acid content was examined in the U87-MG human glioma grown as cultured cells and as a xenograft in severe combined imunodeficiency (SCID) mice. The cultured cells and the xenograft possessed N-glycolylneuraminic acid (NeuGc)-containing gangliosides, despite the inability of human cells to synthesize NeuGc. Human cells express only N-acetylneuraminic acid (NeuAc)-containing gangliosides, whereas mouse cells express both NeuAc- and NeuGc-containing gangliosides. Small amounts of NeuGc ganglioside sialic acid (2-3% of total ganglioside sialic acid) were detected in the cultured cells, whereas large amounts (66% of total ganglioside sialic acid) were detected in the xenograft. The NeuGc in gangliosides of the cultured cells was derived from gangliosides in the fetal bovine serum of the culture medium, whereas that in the U87-MG xenograft was derived from gangliosides of the SCID host. The chromatographic distribution of U87-MG gangliosides differed markedly between the in vitro and in vivo growth environments. The neutral glycosphingolipids in the U87-MG cells consisted largely of glucosylceramide, galactosylceramide, and lactosylceramide, and their distribution also differed in the two growth environments. Asialo-GM1 (Gg4Cer) was not present in the cultured tumor cells but was expressed in the xenograft, suggesting an origin from infiltrating cells (macrophages) from the SCID host. The infiltration of mouse host cells and the expression of mouse sialic acid on human tumor cell glycoconjugates may alter the biochemical and immunogenic properties of xenografts.

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