Ganglioside composition of a mouse brain tumor grown in the severe combined immunodeficiency (SCID) mouse

Seyfried, Thomas N.; El-Abbadi, Mohga; Ecsedy, Jeffrey; Griffin, Mary E.; Yohe, Herbert C.

doi:10.1007/bf02815857

Cited by 6 publications

(10 citation statements)

References 33 publications

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“…We previously showed that most NeuGc-containing gangliosides present in mouse brain tumours and in human glioma xenografts are derived from tumour-associated host cells (macrophages) and from the mouse serum (Ecsedy et al, , 1999Seyfried et al, 1998). Since most NeuGc-containing gangliosides in mouse serum are synthesized in the liver (Cotterchio and Seyfried, 1994), we suggest that the marked reduction of NeuG-containing gangliosides in the i.c.-grown brain tumours results in large part from the NB-DNJ-induced inhibition of ganglioside biosynthesis in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…GM3 is the only ganglioside synthesized by cultured EPEN cells, while gangliosides in the 'a' metabolic pathway (GM3, GM2, GM1, GD1a) are the major gangliosides synthesized by cultured CT-2A cells. Most other gangliosides in the tumours are derived from tumour-infiltrating host cells or from the serum (Seyfried et al, 1996;Ecsedy et al, 1998;Seyfried et al, 1998). The significant reduction in total ganglioside content in the NB-DNJ-treated tumours (Table 1) was associated with a noticeable shift in ganglioside distribution from the structurally simple (GM3) to the structurally complex gangliosides (GD1a, GT1b) ( Figure 5).…”

Section: Influence Of Nb-dnj On Tumour Liver and Brain Ganglioside Dmentioning

confidence: 96%

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N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

et al. 2001

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Abnormalities in glycosphingolipid (GSL) biosynthesis have been implicated in the oncogenesis and malignancy of brain tumours. GSLs comprise the gangliosides and the neutral GSLs and are major components of the cell surface glycocalyx. N -butyldeoxynojirimycin ( N B-DNJ) is an imino sugar that inhibits the glucosyltransferase catalysing the first step in GSL biosynthesis. The influence of N B-DNJ was studied on the growth and ganglioside composition of two 20-methylcholanthrene-induced experimental mouse brain tumours, EPEN and CT-2A, which were grown in vitro and in vivo. N B-DNJ (200 μM) inhibited the proliferation of the EPEN and CT-2A cells by 50%, but did not reduce cell viability. The drug, administered in the diet (2400 mg kg −1 ) to adult syngeneic C57BL/6 mice, reduced the growth and ganglioside content of subcutaneous and intracerebral EPEN and CT-2A tumours by at least 50% compared to the untreated controls. N B-DNJ treatment also shifted the relative distribution of tumour gangliosides in accordance with the depletion of metabolic substrates. Side effects of N B-DNJ treatment were generally mild and included reductions in body and spleen weights and intestinal distension. We conclude that N B-DNJ may inhibit tumour growth through an effect on ganglioside biosynthesis and may be useful as a new chemotherapy for brain tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

Section: Influence Of Nb-dnj On Tumour Liver and Brain Ganglioside Dmentioning

confidence: 96%

N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

et al. 2001

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“…In marked contrast to the U87‐MG xenograft, only trace levels of NeuGc‐containing gangliosides were found in the U87‐MG cultured cells. Previous studies showed that low levels of NeuGc‐containing gangliosides in cultured mouse and human tumor cells were derived exogenously from NeuGc‐containing gangliosides in bovine serum (Hof and Faillard, 1973; Furukawa et al, 1988; El‐Abbadi and Seyfried, 1994; Seyfried et al, 1998). Kawashima and co‐workers (1993) also found that NeuGc‐containing gangliosides in human melanoma xenografts grown in nude mice were derived from the uptake and metabolism of NeuGc‐containing gangliosides present in the nude mouse plasma.…”

Section: Discussionmentioning

confidence: 99%

“…The GSL composition of brain tumors differs markedly from that of normal brain. This arises from GSL abnormalities in proliferating tumor cells and from tumor‐infiltrating host cells (Seyfried et al, 1996, 1998). The enrichment of GSLs on the cell surface and their considerable structural diversity make them potential targets for tumor immunotherapy and diagnosis (Irie and Morton, 1986; Murray et al, 1994, 1996; Sung et al, 1994; Wikstrand et al, 1994 a , b ; Suetake et al, 1995; Uttenreuther Fischer et al, 1995; Nishinaka et al, 1996).…”

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confidence: 99%

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

Ecsedy

Holthaus

Yohe

et al. 1999

Journal of Neurochemistry

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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. Key Words: Oligodendroglioma-Astrocytoma-N-Glycolylneuraminic acid-Brain tumor-Asialo-GM1.

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“…Subcutaneous injection of an experimental ependymoma incapable of synthesizing endogenous GM2(Neu5Gc) results in a tumor that contains GM2 (Neu5Gc) as well other gangliosides suggestive of the presence of Neu5Gc-expressing macrophages [89]. These Neu5Gc-containing gangliosides are still found when the cells are injected into mice with severe combined immune deficiency (SCID), which have no B or T lymphocytes, further suggesting that the gangliosides present do originate from tissue macrophages and/or from metabolic uptake by the tumor cells [90]. To date, no characterization of naturally occurring neural tumors has demonstrated endogenous Neu5Gc synthesis.…”

Section: Claims For Presence Of Neu5gc In Neural Tissuesmentioning

confidence: 99%

Why Is N-Glycolylneuraminic Acid Rare in the Vertebrate Brain?

Davies

Varki

2013

Topics in Current Chemistry

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The sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) differ by a single oxygen atom and are widely found at the terminal position of glycans on vertebrate cell surfaces. In animals capable of synthesizing Neu5Gc, most tissues and cell types express both sialic acids, in proportions that vary between species. However, it has long been noted that Neu5Gc is consistently expressed at trace to absent levels in the brains of all vertebrates studied to date. Although several reports have claimed to find low levels of Neu5Gc-containing glycans in neural tissue, no study definitively excludes the possibility of contamination with glycans from non-neural cell types. This distribution of a molecule – prominently but variably expressed in extraneural tissues but very low or absent in the brain – is, to our knowledge, unique. The evolutionarily conserved brain-specific suppression of Neu5Gc may indicate that its presence is toxic to this organ; however, no studies to date have directly addressed this very interesting question. Here we provide a historical background to this issue and discuss potential mechanisms causing the suppression of Neu5Gc expression in brain tissue, as well as mechanisms by which Neu5Gc may exert the presumed toxicity. Finally, we discuss future approaches towards understanding the mechanisms and implications of this unusual finding.

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Ganglioside composition of a mouse brain tumor grown in the severe combined immunodeficiency (SCID) mouse

Cited by 6 publications

References 33 publications

N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

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

Why Is N-Glycolylneuraminic Acid Rare in the Vertebrate Brain?

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