Dataset Information

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

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.

SUBMITTER: Grande S

PROVIDER: S-EPMC5835274 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Grande Sveva S Palma Alessandra A Ricci-Vitiani Lucia L Luciani Anna Maria AM Buccarelli Mariachiara M Biffoni Mauro M Molinari Agnese A Calcabrini Annarica A D'Amore Emanuela E Guidoni Laura L Pallini Roberto R Viti Vincenza V Rosi Antonella A

Stem cells international 20180218

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 ...[more]

PMID: 29531533

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Project description:To build a framework for investigation of the associations between imaging, clinical target volumes (CTVs), and metabolic tumor volumes (MTVs) features for better understanding of the underlying information in the CTVs and dependencies between these volumes. High-throughput extraction of imaging and metabolomic quantitative features from magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging of glioblastoma multiforme (GBM) results in tens of variables per patient. In radiation therapy of GBM the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl aspartate (NAA) and choline (Cho). The corresponding clinical target volumes (CTVs) for radiation therapy are based on contrast-enhanced T1-weighted (CE-T1w) and T2-weighted (T2w)/fluid-attenuated inversion recovery MRI.Necrotic portions, enhancing lesion, and edema were manually contoured on CE-T1w/T2w images for 17 GBM patients. Clinical target volumes and MTVs for NAA (MTVNAA) and Cho (MTVCho) were constructed. Imaging and metabolic features related to size, shape, and signal intensities of the volumes were extracted. Tumors were also scored categorically for 10 semantic imaging traits by a neuroradiologist. All features were investigated for redundancy. Two-way correlations between imaging and CTVs/MTVs features were visualized as heatmaps. Associations between MTVNAA and MTVCho and imaging features were studied using Spearman correlation.Forty-eight imaging features were extracted per patient. Half of the imaging traits were replaced with automatically extracted continuous variables. Twenty features were extracted from CTVs and MTVs. A series of semantic imaging traits were replaced with automatically extracted continuous variables. There were multiple (22) significant correlations of imaging measures with CTVs/MTVNAA, whereas there were only 6 with CTVs/MTVCho.A framework for investigation of codependencies between MRI and magnetic resonance spectroscopic imaging radiomic features and CTVs/MTVs has been established. The MTV for NAA was found to be closely associated with MRI volumes, whereas very few imaging features were related to MTVCho, indicating that Cho provides additional information to imaging.

Dataset Information

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

Publications

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

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