Recent progress in O-acetylated gangliosides analysis and functions in cancer

Gangliosides are acidic glycosphingolipids substituted by one or more sialic acid residues. The expression of complex gangliosides from b- and c-series, which are characterized by the presence of at least two sialic acid residues linked to lactosylceramide, is limited to the nervous system in healthy adults. However, complex gangliosides are re-expressed in several diseases including neuro-ectoderm derived cancers and associated with a poor prognosis for patients. Moreover, sialic acid residues of gangliosides can be acetylated, modulating ganglioside functions and immunogenicity. Due to the lability of acetyl groups, the acetylation of gangliosides has often been overlooked in ganglioside analyses, the acetylation of gangliosides being only evaluated by immunological methods. Recent methods of extraction and ionization were developed in order to preserve the O-acetylation of gangliosides for mass spectrometry analysis, giving a more precise definition of ganglioside O-acetylation in human cancers. After summarizing our current knowledge of O-acetylated ganglioside expression and biosynthesis, we will focus on the analytical methods that have been developed for their analysis. The use of O-acetylated gangliosides as targets for cancer immunotherapy will be also discussed.