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Mass Spectrometric Determination of Ganglioside Expression and Structure in Glioblastoma Multiforme and Surrounding Brain Tissue

Oncogenic transformations are accompanied by aberrant glycosphingolipid metabolism. Gangliosides are sialylated glycosphingolipids highly enriched in cell surface microdomains and involved in cell-cell and cell-matrix interactions. Their concentration is the highest in adult human brain gray matter being 10 to 100 times higher than in extraneural tissue. Gangliosides influence tumor growth and progression by modulation of tumor cells adhesion, migration and angiogenesis, so altered ganglioside composition in tumor cells may have important role in metastatic and invasive properties of tumor cells. Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor presumably originating from neuroglial progenitor cells. The aim of this study is to accomplish detailed characterization of ganglioside composition in pathohistologically defined GBM and to compare it with surrounding brain tissue in order to identify biomarker species related to pathological changes in the brain. Compositional and structural analysis of ganglioside content from GBM and the surrounding area was performed. Total gangliosides were isolated and purified as native mixtures from tissue homogenates and spectrophotometrically quantified. HPTLC was used for compositional analysis. MS screening and sequencing analyses were carried out on an ESI Ion Trap mass spectrometer (AmaZon Speed Series, Bruker Daltonics). The total ganglioside content determined in the tumor sample was approximately 5 times lower than in the normal human brain and 2 times lower than in the tissue surrounding the tumor. The HPTLC ganglioside pattern of tumor sample was highly distinctive from the normal and surrounding tissue. MS analysis of the tumor revealed complex ganglioside composition, especially differing from the surrounding tissue in the content of GD3 ganglioside species and confirming the presence of species previously reported as tumor-associated ones. Changes in ganglioside composition which occur in correlation with tumor pathology could be of potential diagnostic and/or prognostic value and serve as a platform for development of antitumor therapeutics.

gangliosides ; glioblastoma multiforme ; mass spectrometry

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