Ganglioside composition of human neuroblastomas correlation with prognosis A pediatric oncology group study

Schengrund, Cara Lynne; Repman, Mary Ann; Shochat, Stephen J.

doi:10.1002/1097-0142(19851201)56:11<2640::aid-cncr2820561118>3.0.co;2-w

Cited by 36 publications

(17 citation statements)

References 18 publications

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“…Thus, predominant expression of complex gangliosides can be considered a biochemical marker of increasing neuronal differentiation. Further, the retinoic acid-induced changes in the ganglioside, complement of NB cell lines, are analogous to reported differences in CbG content among prognostically distinct categories of NB tumours (Schengrund et al, 1985;Schengrund and Shochat, 1988;Hettmer et al, 2003). Specifically, we previously found that among 74 human NB tumours, high (X35%) CbG expression (a) characterised nonprogressive vs progressive tumours (median 41 vs 18% of total gangliosides), and (b) was strongly predictive of a favourable outcome, even when other prognostic factors were considered (Hettmer et al, 2003).…”

Section: Discussionsupporting

confidence: 72%

“…The impetus for this study were our findings (Hettmer et al, 2003) and those of others (Schengrund et al, 1985;Sung et al, 1995;Yates et al, 1999), suggesting that differences in tumour tissue CbG (GD1b, GT1b and GQ1b) expression are linked to the clinical and biological behaviour of NB and other tumours. In order to obtain an in vitro model that permits a more dynamic view of NB ganglioside biosynthesis, we analysed ganglioside expression in four well-described NB cell lines, LAN-1, LAN-5, SMS-KCNR and SMS-KCN.…”

Section: Ganglioside Expression In Human Nb Cell Linessupporting

confidence: 51%

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Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid

et al. 2004

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Recent findings link increased expression of the structurally complex 'b' pathway gangliosides GD1b, GT1b, GQ1b (CbG) to a favourable clinical and biological behaviour in human neuroblastoma (NB). Seeking a model to probe these observations, we evaluated four human NB cell lines. Very low CbG content (4 -10%) in three of the four cell lines (LAN-5, LAN-1, SMS-KCNR) reflected the ganglioside pattern observed in the most aggressive NB tumours. Pharmacological alterations of complex ganglioside synthesis in vitro by a 5 -7 day exposure to 5 -10 mM retinoic acid, which is employed in maintenance therapy of disseminated NB, included markedly increased (i) relative expression of CbG (6.672.0-fold increase, P ¼ 0.037), (ii) relative expression of the analogous 'a' pathway gangliosides, termed CaG (6.471.4-fold increase in GM1a and GD1a; P ¼ 0.010), and (iii) total cellular ganglioside content (2.0 -6.3-fold), which in turn amplified the accumulation of structurally complex gangliosides. Substantial increases (2.7 -2.9-fold) in the activity of GD1b/GM1a synthase (b-1,3-galactosyltransferase), which initiates the synthesis of CbG and CaG, accompanied the all-trans retinoic acid (ATRA)-induced ganglioside changes. Thus, increased CbG synthesis in NB cell lines is attributable to a specific effect of ATRA, namely induction of GD1b/GM1a synthase activity. Since the shift towards higher expression of CbG and CaG during retinoic acid-induced cellular differentiation reflects a ganglioside pattern found in clinically less-aggressive tumours, our studies suggest that complex gangliosides may play a role in the biological and clinical behaviour of NB.

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Section: Discussionsupporting

confidence: 72%

Section: Ganglioside Expression In Human Nb Cell Linessupporting

confidence: 51%

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid

et al. 2004

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“…It is very interesting that low (≤35%) or absent expression of gangliosides of the complex “b” (CbG) pathway (GD1b, GT1b, and GQ1b) correlates with an aggressive biological phenotype in human NB tumors (21). This observation is consistent with reports in which a decreased or absent expression of two CbG subspecies, GD1b and GT1b, was linked to reduced survival in NB patients (22, 23). High expression of complex gangliosides, both complex “a” gangliosides (CaG) and CbG, has been shown to inhibit aggressive tumor-cell behavior in vitro (e.g., cellular proliferation and migration) and to enhance differentiation (24, 25).…”

Section: Gangliosidessupporting

confidence: 93%

Glycobiology of Neuroblastoma: Impact on Tumor Behavior, Prognosis, and Therapeutic Strategies

Berois

Osinaga

2014

Front. Oncol.

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Neuroblastoma (NB), accounting for 10% of childhood cancers, exhibits aberrant cell-surface glycosylation patterns. There is evidence that changes in glycolipids and protein glycosylation pathways are associated to NB biological behavior. Polysialic acid (PSA) interferes with cellular adhesion, and correlates with NB progression and poor prognosis, as well as the expression of sialyltransferase STX, the key enzyme responsible for PSA synthesis. Galectin-1 and gangliosides, overexpressed and actively shedded by tumor cells, can modulate normal cells present in the tumor microenvironment, favoring angiogenesis and immunological escape. Different glycosyltransferases are emerging as tumor markers and potential molecular targets. Immunotherapy targeting disialoganglioside GD2 rises as an important treatment option. One anti-GD2 antibody (ch14.18), combined with IL-2 and GM-CSF, significantly improves survival for high-risk NB patients. This review summarizes our current knowledge on NB glycobiology, highlighting the molecular basis by which carbohydrates and protein–carbohydrate interactions impact on biological behavior and patient clinical outcome.

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“…Previous studies have defined the ganglioside carbohydrate species that are expressed and shed by neuroblastoma cells, and strongly support a link between expression of certain ganglioside molecules and the behavior of this tumor [2][3][4][5][6][10][11][12]. Firstly, overexpression of GD2 distinguishes neuroblastoma from benign neural tumors [10].…”

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confidence: 99%

Low complex ganglioside expression characterizes human neuroblastoma cell lines

2005

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Low (≤35%) or absent expression of the complex 'b' pathway gangliosides GD1b, GT1b and GQ1b (CbG) correlates with an aggressive biological phenotype in human neuroblastoma tumors. To develop an in vitro model to probe mechanisms by which CbG may contribute to neuroblastoma behavior, we have comprehensively evaluated ganglioside expression in nine well-established human neuroblastoma cell lines, all derived from poor prognosis tumors. Total cellular ganglioside content ranged from 8 to 69 nmol/10 8 cells. High performance thin layer chromatography revealed that the simple disialoganglioside GD2 was prominent in eight of the cell lines (up to 60% of total gangliosides), whereas CbG were low (1-21%) in all nine cell lines. The structurally most complex 'b' pathway species, GQ1b, was not detected in any of the cell lines. The prominence of GD2 in neuroblastoma cell lines mirrors the high expression of GD2 that characterizes human neuroblastoma tumors, and the low CbG expression in the cell lines is analogous to that found in clinically and biologically unfavorable neuroblastoma tumors, thus establishing these neuroblastoma cell lines as valuable model systems for study of the role of CbG in the pathobiology of human neuroblastoma.

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Ganglioside composition of human neuroblastomas correlation with prognosis A pediatric oncology group study

Cited by 36 publications

References 18 publications

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid

Glycobiology of Neuroblastoma: Impact on Tumor Behavior, Prognosis, and Therapeutic Strategies

Low complex ganglioside expression characterizes human neuroblastoma cell lines

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