title: Aberrant ganglioside composition in glioblastoma multiforme and peritumoral tissue: A mass spectrometry characterization.
abstract: Tumor cells are characterized by aberrant glycosylation of the cell surface glycoconjugates. Gangliosides are sialylated glycosphingolipids highly abundant in neural tissue and considered as tumor markers and therapeutic targets. In this study, a detailed characterization of native ganglioside mixtures from glioblastoma multiforme, corresponding peritumoral tissue and healthy human brain was performed using mass spectrometry and high performance thin layer chromatography in order to elucidate their roles as tumor-associated antigens. Distinctive changes in ganglioside expression were determined in glioblastoma compared to healthy brain tissue showing 5 times lower total ganglioside content and higher abundance of simple gangliosides. Glioblastoma gangliosides were characterized by highly diverse ceramide composition with fatty acyl chains varying from 16 to 24 carbon atoms, while in normal and peritumoral tissue mostly C18 chains were found. The most abundant ganglioside in glioblastoma was GD3 (d18:1/18:0), followed by GD3 (d18:1/24:0) that was exclusively detected in glioblastoma tissue. Peritumoral tissue expressed higher abundance of GD3- and nLM1/GM1-species while lower GT1-species vs. normal brain. O-Ac-GD1, known as neurostatin, was detected in normal and peritumoral tissue, but not in glioblastoma. O-Ac-GD3 species were found exclusively in glioblastoma; MS structural characterization of the isomeric form possessing the O-acetylation at the inner sialic acid residue confirmed our previous finding that this isomer is glioma-associated. This, to our knowledge, the most detailed characterization of ganglioside composition in glioblastoma and peritumoral tissue, especially addressing the ceramide variability and O-acetylation of tumor-associated gangliosides, could contribute to recognition of new molecular targets for glioblastoma treatment and sub-classification.
authors.affiliation: Department of Chemistry and Biochemistry, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia. Electronic address: dragana.fabris@mef.hr.
authors.forename: Dragana
authors.initials: D
authors.lastname: Fabris
authors.affiliation: Department of Physical Chemistry, Ruđer Bošković Institute, 1000 Zagreb, Croatia. Electronic address: marko@irb.hr.
authors.forename: Marko
authors.initials: M
authors.lastname: Rožman
authors.affiliation: Department of Neurosurgery, University Hospital Center "Sestre Milosrdnice", 10000 Zagreb, Croatia. Electronic address: neurosajko@gmail.com.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Sajko
authors.affiliation: Department of Chemistry and Biochemistry, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia. Electronic address: zeljka.vukelic@mef.hr.
authors.forename: Željka
authors.initials: Ž
authors.lastname: Vukelić
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D002855:Chromatography, Thin Layer; D005260:Female; D005732:Gangliosides / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D005732:Gangliosides
keywords: Biomarkers; Gangliosides; Glioblastoma; Mass spectrometry; Peritumoral tissue