Shedding of G_D2 ganglioside by human neuroblastoma

Abstract

Substantial concentrations of the cell-surface glycosphingolipid, the disialoganglioside GD2, are uniformly present in human neuroblastoma tumors. This ganglioside can also be detected in the plasma of patients with neuroblastoma by direct thin-layer chromatographic analysis. Among 32 neuroblastoma patients in all clinical stages studied prior to the initiation of treatment, 27 (84%) showed measurably elevated plasma concentrations of GD2 (greater than or equal to 50 pmol/ml). The mean level (545 +/- 108 pmol/ml) was more than 50 times the normal plasma GD2 concentration of less than or equal to 10 pmol/ml. Circulating GD2 was not detected in the plasma of patients with the related, more differentiated tumors, ganglioneuroblastoma and ganglioneuroma, indicating an association of the shedding of this ganglioside with the undifferentiated phenotype. Circulating GD2 diminished in patients in response to therapy, and reappeared in patients whose disease recurred. The results suggest that the sequential determination of circulating GD2 will be of value in monitoring individual patients with neuroblastoma.

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

“…ubiquitously high expression of GD2 that characterizes NB tumours (Wu et al, 1986). Importantly, the low CbG expression observed in each of the cell lines is also analogous to the CbG levels found in clinically and biologically unfavourable NB tumours (Hettmer et al, 2003).…”

“…Gangliosides are overexpressed and actively shed by tumour cells (Wu et al, 1986;Valentino et al, 1990;Li and Ladisch, 1991) and have a number of biological properties that could conceivably alter tumour-host interactions to influence the survival of the malignant cells that carry these molecules (Hakomori, 1996). Our previous studies have linked specific ganglioside changes in human NB tumours to differences in the clinical and biological behaviour of this tumour (Kaucic et al, 2001;Hettmer et al, 2003), and raise the possibility that pharmacologically induced modulation of NB ganglioside content could have important consequences for outcome.…”

“…Our previous studies have characterised ganglioside expression in human NB, a paediatric malignancy of neural crest origin (Wu et al, 1986;Valentino et al, 1990;Kaucic et al, 2001;Hettmer et al, 2003). We have linked alterations in the expression of complex 'b' pathway gangliosides (CbG) downstream of GD1b/GM1a synthase (GD1b, GT1b and GQ1b) to differences in the biological phenotype and clinical behaviour that can be used to predict patient outcome in NB (Hettmer et al, 2003).…”

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

“…Overexpression of GD2 ganglioside distinguishes neuroblastoma from benign neural tumors (11), which has resulted in the application of antibodies targeting the carbohydrate in the diagnosis of localized and metastatic neuroblastoma and in the monitoring of therapy response and minimal residual disease (12,13). The fact that approximately 60% of children with neuroblastoma, which is the most common extracranial neoplasm of childhood, have high-risk tumors that can rarely be cured by conventional therapy, stresses the need for new treatment protocols to control minimal residual disease.…”

Neuroblastoma cells can be classified according to glycosphingolipid expression profiles identified by liquid chromatography-tandem mass spectrometry

“…For example, NB cells express a higher level of GD2 than normal brain cells do (10). Characterization of ganglioside expression in the NBs of infants has revealed higher total pathway b ganglioside levels than in older children (8).…”