Ganglioside Content and Composition in Human Gliomas

Gaini, S. M.; Riboni, Laura; Cerri, C.; Grimoldi, N.; Sganzerla, Erik P.; Berra, B.

doi:10.1007/978-3-7091-8978-8_27

Cited by 10 publications

(12 citation statements)

References 16 publications

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“…1). Previous studies have shown that malignant gliomas have high levels of GD3, and its expression correlates with the degree of malignancy [8,9]. As shown by immunofluorescent confocal microscopy, our present results also revealed that the levels of the ganglioside GD3 markedly increased in T98G and U-87MG cells when compared with SK-N-BE(2)-C cells.…”

Section: Discussionsupporting

confidence: 75%

“…Many previous studies showed that aberrant ganglioside expression was strongly associated with the malignancy of tumor cells and that tumor-associated gangliosides played a crucial role in the induction of tumor cell invasion and metastasis [3,4]. It was also known that the composition and the content of gangliosides changed during physiological growth and differentiation as well as in neoplastic cell transformation [5][6][7][8][9]. In addition, changes in the composition and the content of gangliosides have been observed in human gliomas, which are the most common form of human primary brain tumor [9 -11].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have demonstrated that malignant gliomas contain a higher concentration of GD3, and its expression correlates with the degree of malignancy [8,9]. GD3 is synthesized by GD3 synthase (ST8Sia I; EC 2.4.99.8), which is a key enzyme for the synthesis of whole b-series gangliosides including GD2 in addition to GD3 itself [12].…”

Section: Introductionmentioning

confidence: 99%

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Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (<italic>hST8Sia I</italic>) gene

Dae¹,

Kwon²,

Kang³

et al. 2009

ABBS

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We identified the promoter region of the human GD3 synthase (hST8Sia I) gene to elucidate the mechanism underlying the regulation of hST8Sia I expression in human glioblastoma cells. The 5 0 -rapid amplification of cDNA end using mRNA prepared from U-87MG cells revealed the presence of transcription start site of hST8Sia I gene, and the 5 0 -terminal analysis of its product showed that transcription started from 648 nucleotides upstream of the translational initiation site. Functional analysis of the 5 0 -flanking region of the hST8Sia I gene by transient expression method revealed that the region from 2638 to 2498 is important for transcriptional activity of the hST8Sia I gene in U-87MG and T98G cells. This region lacks apparent TATA and CAAT boxes, but contains putative binding sites for transcription factors AREB6 and Elk-1. Sitedirected mutagenesis and transient transfection assays demonstrated that both AREB6 and Elk-1 elements in this region were required for the promoter activity in U-87MG and T98G cells. These results indicated that both AREB6 and Elk-1 might play an essential role in the transcriptional activity of hST8Sia I gene essential for GD3 synthesis in human glioblastoma cells.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (<italic>hST8Sia I</italic>) gene

Dae¹,

Kwon²,

Kang³

et al. 2009

ABBS

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“…Dramatic abnormalities in ganglioside composition and concentration are associated with neural tumor development in humans. In general, tumors classified as gliomas express elevations of the structurally less complex gangliosides (GM3 and GD3) and reductions of the structurally more complex gangliosides (Yates et al, 1979;Traylor and Hogan, 1980;Eto and Shinoda, 1982;Berra et al, 1983Berra et al, , 1985Fredman, 1988;Fredman et al, 1988;Gaini et al, 1988;Gottfries et al, 1990;Jennemann et al, 1990). Tumors classified as neuroblastomas, on the other hand, usually express lower levels of GM3 and elevations of GD2 and oligosialogangliosides, (Schulz et al, 1984;Schengrund et al, 1985;Wu et al, 1986;Shochat et al, 1987;Ladish, 1989;Yates, 1988).…”

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confidence: 99%

Ganglioside distribution in murine neural tumors

Seyfried

El-Abbadi

Roy

1992

Molecular and Chemical Neuropathology

111

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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 to N-acetylneuraminic acid (NeuAc), the gangliosides in the solid tumors contained significant amounts of N-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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“…In cancers, GD3 is highly accumulated in human primary melanoma tissues as well as in established melanoma cell lines (26), whereas human normal melanocytes express no or minimal levels of GD3 (27). Moreover, malignant gliomas contain higher levels of GD3, and its expression correlates with the degree of malignancy (28). GD3 is produced from the precursor GM3 by the activity of GD3 synthase (GD3S), which mediates the properties of CSCs through the c-MET signaling pathway and correlates with poor prognosis in triple-negative human breast tumors (29).…”

mentioning

confidence: 99%

Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity

Yeh

Wang

Lou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The cancer stem cells (CSCs) of glioblastoma multiforme (GBM), a grade IV astrocytoma, have been enriched by the expressed marker CD133. However, recent studies have shown that CD133 − cells also possess tumor-initiating potential. By analysis of gangliosides on various cells, we show that ganglioside D3 (GD3) is overexpressed on eight neurospheres and tumor cells; in combination with CD133, the sorted cells exhibit a higher expression of stemness genes and self-renewal potential; and as few as six cells will form neurospheres and 20-30 cells will grow tumor in mice. Furthermore, GD3 synthase (GD3S) is increased in neurospheres and human GBM tissues, but not in normal brain tissues, and suppression of GD3S results in decreased GBM stem cell (GSC)-associated properties. In addition, a GD3 antibody is shown to induce complementdependent cytotoxicity against cells expressing GD3 and inhibition of GBM tumor growth in vivo. Our results demonstrate that GD3 and GD3S are highly expressed in GSCs, play a key role in glioblastoma tumorigenicity, and are potential therapeutic targets against GBM.GBM | ST8SIA1 | gangliosides | glycosphingolipids | cancer stem cells

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Ganglioside Content and Composition in Human Gliomas

Cited by 10 publications

References 16 publications

Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (<italic>hST8Sia I</italic>) gene

Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (<italic>hST8Sia I</italic>) gene

Ganglioside distribution in murine neural tumors

Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity

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Ganglioside Content and Composition in Human Gliomas

Cited by 10 publications

References 16 publications

Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (&lt;italic&gt;hST8Sia I&lt;/italic&gt;) gene

Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (&lt;italic&gt;hST8Sia I&lt;/italic&gt;) gene

Ganglioside distribution in murine neural tumors

Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity

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Product

Resources

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Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (<italic>hST8Sia I</italic>) gene

Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (<italic>hST8Sia I</italic>) gene