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Qualitative and quantitative characterization of sphingoid bases in glioblastoma multiforme and healthy human brain tissue

Sphingoid bases are structural components of membrane sphingolipids, but also function as signaling molecules influencing cell proliferation, migration and cell death. Changes in sphingolipid metabolism are present in different pathological processes such as neurodegeneration and cancer. Glioblastoma multiforme (GBM) is the most aggressive and the most common type of glioma. GBM cells are highly infiltrative and therefore the treatment of this brain tumor is still very poor with the prognosis of maximum 18 months after the confirmed diagnosis. The aim of this work was to analyze the composition of sphingoid bases of GBM and healthy human brain tissue, isolated following acid hydrolysis of the tissue lipid fraction containing more complex neutral sphingolipids (neutral glycosphingolipids, sphingomyelins, ceramides) and presumably free sphingoid bases. Isolated sphingoid bases were analyzed by highperformance liquid chromatography (HPLC) and high resolution mass spectrometry (MS). In both GBM and healthy brain tissue six different species of sphingoid bases were detected and structurally characterized as d16:1, d17:0, d18:2, d18:1, d18:0 and d20:1. A significantly lower concentration of analyzed total sphingoid bases was detected in GBM compared to the healthy brain tissue. To the authors’ best knowledge the presence of the d16:1, d17:0 and d20:1 sphingoid bases in neutral sphingolipids of human brain tissue have been reported for the first time in this work. Up to now, the d20:1 base has been considered a building component of only the ganglioside ceramide residues of mammalian brain. The results obtained presently show that the composition of sphingoid bases in neutral sphingolipids is far more diverse than the ones previously considered, which then increases the complexity and the number of possible structural forms of neutral sphingolipid species present in the human brain as well as in the brain tumors. Significantly lower concentrations of sphingoid bases found in the GBM vs. healthy brain tissue indicate the changes in sphingolipid metabolism occurring in the tumor cells. These findings may help in elucidating the sphingolipid roles in tumor transformations and suggesting new approaches in improvement of GBM treatment.

sphingoid bases ; glioblastoma ; mass spectrometry ; HPLC

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