Ceramide Composition in Exosomes for Characterization of Glioblastoma Stem-Like Cell Phenotypes.
Autor: Melero-Fernandez de Mera, Raquel M.; Villaseñor, Alma; Rojo, David; Carrión Navarro, Josefa; Gradillas, Ana; Ayuso Sacido, Ángel; Barbas, Coral
Resumen: Glioblastoma (GBM) is one of the most malignant central nervous system tumor types.
Comparative analysis of GBM tissues has rendered four major molecular subtypes. From
them, two molecular subtypes are mainly found in their glioblastoma cancer stem-like cells
(GSCs) derived in vitro: proneural (PN) and mesenchymal (MES) with nodular (MES-N) and
semi-nodular (MES-SN) disseminations, which exhibit different metabolic, growth, and
malignancy properties. Many studies suggest that cancer cells communicate between
them, and the surrounding microenvironment, via exosomes. Identifying molecular
markers that allow the specific isolation of GSC-derived exosomes is key in the
development of new therapies. However, the differential exosome composition
produced by main GSCs remains unknown. The aim of this study was to determine
ceramide (Cer) composition, one of the critical lipids in both cells and their cell-derived
exosomes, from the main three GSC phenotypes using mass spectrometry-based
lipidomics. GSCs from human tissue samples and their cell-derived exosomes were
measured using ultra-high-performance liquid chromatography-quadrupole time-of-flight
mass spectrometry (UHPLC/Q-TOF-MS) in an untargeted analysis. Complete
characterization of the ceramide profile, in both cells and cell-derived exosomes from
GSC phenotypes, showed differential distributions among them. Results indicate that
such differences of ceramide are chain-length dependent. Significant changes for the C16
Cer and C24:1 Cer and their ratio were observed among GSC phenotypes, being different
for cells and their cell-derived exosomes.
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