Metabolic heterogeneity evidenced by MRS among patient-derived glioblastoma multiforme stem-like cells accounts for cell clustering and different responses to drugs

Sveva Grande, Alessandra Palma, Lucia Ricci-Vitiani, Anna Maria Luciani, Mariachiara Buccarelli, Mauro Biffoni, Agnese Molinari, Annarica Calcabrini, Emanuela D'Amore, Laura Guidoni, Roberto Palni, Vincenza Viti, Antonella Rosi

Research output: Contribution to journalArticle

Abstract

Clustering of patient-derived glioma stem-like cells (GSCs) through unsupervised analysis of metabolites detected by magnetic resonance spectroscopy (MRS) evidenced three subgroups, namely clusters 1a and 1b, with high intergroup similarity and neural fingerprints, and cluster 2, with a metabolism typical of commercial tumor lines. In addition, subclones generated by the same GSC line showed different metabolic phenotypes. Aerobic glycolysis prevailed in cluster 2 cells as demonstrated by higher lactate production compared to cluster 1 cells. Oligomycin, a mitochondrial ATPase inhibitor, induced high lactate extrusion only in cluster 1 cells, where it produced neutral lipid accumulation detected as mobile lipid signals by MRS and lipid droplets by confocal microscopy. These results indicate a relevant role of mitochondrial fatty acid oxidation for energy production in GSCs. On the other hand, further metabolic differences, likely accounting for different therapy responsiveness observed after etomoxir treatment, suggest that caution must be used in considering patient treatment with mitochondria FAO blockers. Metabolomics and metabolic profiling may contribute to discover new diagnostic or prognostic biomarkers to be used for personalized therapies.

Original languageEnglish
Article number3292704
JournalStem Cells International
Volume2018
DOIs
Publication statusPublished - Jan 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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