engleski

Mass Spectrometry-Based Characterization of Gangliosides from Selected Brain Tumors : Further Evidences of Aberrant Glycosylation

Virtually all tumor transformed cells seem to possess aberrant cell-surface glycosylation patterns influencing tumor progression, metastasis and invasivity. The patterns consist of surface-expressed membrane-building glycoconjugates, including gangliosides (GGs), sialylated glycosphingolipids (GSLs). Gangliosides are highly abundant in brain. Their composition is markedly altered in various brain tumors but even so specific for the tumor type, changing in correlation with a tumor grade and invasiveness. Some malignant brain tumors shed GGs that can be detected in patient serum and cerebrospinal fluid. GGs modulate adhesion and migration of tumor cells, as well as angiogenesis, and consequently tumor growth and progression. Moreover, some GG species are capable to inhibit growth (proliferation) or to induce apoptosis of cancer cells. Modulation of the synthesis of specific glioma-associated GSLs alters tumor invasivity [1, 2]. Therefore, tumor-associated GGs are intensively studied as potential diagnostic biomarkers and therapeutic targets/agents. Our team participates in investigation of GG role and diagnostic potential in brain tumor pathology. To accomplish detailed and systematic characterization of aberrant GG composition in histopathologically defined brain tumor specimens, we have employed modern mass spectrometric approaches in combination with thin-layer chromatographic and immunochemical methods. In this contribution, the results of compositional analysis of GG mixtures isolated from dysembryoplastic neuroepithelial tumor (DNET) and brain metastasis of adenocarcinoma will be presented. MS screening and sequencing was carried out on a High Capacity Ion Trap Ultra, coupled with fully automated chip-based nanoelectrospray NanoMate robot. The total GG content in DNET sample was approx. 10 times lower than in the normal adult human brain. The GG patterns of both samples revealed by MS and HPTLC were highly distinctive. MS screening confirmed the presence of GG species previously reported as tumor-associated ones (O-acetylated GD3, di-O-Ac-GD3) together with unusual minor species (O-Ac- and di-O-Ac-GD1, -GT1 and -GQ1, Fuc-GQ1, GalNAc-GT2, GalNAc-GT1, O-Ac-GP1 and GH1). The analyzed pattern specificities will be discussed in comparison to the patterns of previously characterized brain tumor specimens (gliosarcoma, meningioma, haemangioma). In conclusion, modern MS-based analytical approaches enable detailed profiling and structural characterization of tumor-associated GGs and are, therefore, the best choice for identification of biomarkers.

gangliosides; brain tumors; aberrant glycosylation; mass spectrometry

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