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Stem Cells International
Volume 2018, Article ID 3292704, 16 pages
https://doi.org/10.1155/2018/3292704
Research Article

Metabolic Heterogeneity Evidenced by MRS among Patient-Derived Glioblastoma Multiforme Stem-Like Cells Accounts for Cell Clustering and Different Responses to Drugs

1National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy
2Istituto Nazionale di Fisica Nucleare INFN Sez. di Roma, 00185 Rome, Italy
3Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
4National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, Italy
5National Centre for Animal Experimentation and Welfare, Istituto Superiore di Sanità, 00161 Rome, Italy
6Institute of Neurosurgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy

Correspondence should be addressed to Antonella Rosi; ti.ssi@isor

Received 10 August 2017; Accepted 5 December 2017; Published 18 February 2018

Academic Editor: Arazdordi Toumadje

Copyright © 2018 Sveva Grande et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.