GANGLIOSIDE GM3 (NEUGC)

Definition

ChEBI: N-glycolylneuraminyllactosylceramide is a sialotriaosylceramide in which the triaosyl group is 3,5-dideoxy-5-(2-hydroxyacetamido)-D-glycero-alpha-D-galacto-non-2-ulopyranonosyl-(2->3)-beta-D-galactopyranosyl-(1->4)-beta-D-glucopyranosyl attached to the primary hydroxy function of ceramide. A tumour antigen found in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but not usually detected in normal human cells. It has a role as a tumour antigen.

Biological Activity

N-glycolyl-Ganglioside GM3 (NeuGc-GM3) is a form of ganglioside GM3 that contains an N-glycolylated sialic acid (NeuGc). It is not biosynthesized in humans under baseline conditions due to a mutation in CMP-Neu5Ac hydroxylase (CMAH), which converts N-acetyl sialic acid to N-glycolyl sialic acid, but NeuGc can be taken up by human cells via the diet and incorporated into glycolipids, such as ganglioside GM3.1,2 NeuGc-GM3 impairs differentiation and maturation of dendritic cells in vitro and reduces CD4 expression in non-activated T cells.1,3 It increases the number of lung tumor nodules formed in a murine Lewis lung carcinoma model.4 It is found in a variety of human cancers, including breast and lung cancers, as well as pediatric cancers.1 Levels of NeuGc-GM3 are negatively correlated with the number of mature dendritic cells in patient-derived non-small cell lung cancer (NSCLC) tumor tissue.5 Anti-NeuGc-GM3 antibodies, able to destroy tumor cells in vitro, have been found in individuals without cancer but not in patients with NSCLC.1,6 N-glycolyl-Ganglioside GM3 mixture contains ganglioside GM3 molecular species with primarily C22:0, C23:0, and C24:0 fatty acyl chain lengths. [Matreya, LLC. Catalog No. 1553]

References

1.Labrada, M., Dorvignit, D., Hevia, G., et al.GM3(Neu5Gc) ganglioside: An evolution fixed neoantigen for cancer immunotherapySemin. Oncol.45(1-2)41-51(2018) 2.Tangvoranuntakul, P., Gagneux, P., Diaz, S., et al.Human uptake and incorporation of an immunogenic nonhuman dietary sialic acidProc. Natl. Acad. Sci. USA100(21)12045-12050(2003) 3.de León, J., Fernández, A., Clavell, M., et al.Differential influence of the tumour-specific non-human sialic acid containing GM3 ganglioside on CD4+CD25- effector and naturally occurring CD4+CD25+ regulatory T cells functionInt. Immunol.20(4)591-600(2008) 4.Segatori, V.I., Vazquez, A.M., Gomez, D.E., et al.Preclinical evaluation of racotumomab, an anti-idiotype monoclonal antibody to N-glycolyl-containing gangliosides, with or without chemotherapy in a mouse model of non-small cell lung cancerFront. Oncol.2160(2012) 5.van Cruijsen, H., Ruiz, M.G., van der Valk, P., et al.Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancerBMC Cancer9180(2009) 6.Rodríguez-Zhurbenko, N., Martínez, D., Blanco, R., et al.Human antibodies reactive to NeuGcGM3 ganglioside have cytotoxic antitumor propertiesEur. J. Immunol.43(3)826-837(2013)