Metabolic heterogeneity among Glioblastoma stem-like cells reflects differences in response to drug treatments.

Research output: Contribution to conferenceAbstract

Abstract

Purpose
Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The cancer stem cell hypothesis postulates the existence within GBM of a small fraction of self-renewing cells with stem like properties (GSCs), resistant to conventional treatments. Metabolic profiling may contribute to discover new diagnostic or prognostic biomarkers to be used for personalized therapies.

Methods
Forty-four GSC lines, derived from GBM patients were analyzed via MR spectroscopy as described in [1]. Unsupervised Cluster analysis of MR data was performed to identify GSC subgroups with different metabolic profiles. Responses to treatment with oligomycin and etomoxir were examined by MRS and confocal microscopy.

Results
Clustering of GSCs evidenced three subgroups: Clusters 1a and 1b, with high intergroup similarity and neural fingerprints, and Cluster 2, with a metabolism typical of commercial tumor lines (Fig. 1) according to [2]. 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 (MRS) and as lipid droplets (confocal microscopy).

Conclusions
These results indicate a relevant role of mitochondrial fatty acids 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.

Original languageEnglish
Pages250-251
Number of pages2
DOIs
Publication statusPublished - Dec 2018

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Glioblastoma
Stem Cells
Pharmaceutical Preparations
Oligomycins
Confocal Microscopy
Lactic Acid
Therapeutics
Lipids
Metabolome
Neoplastic Stem Cells
Dermatoglyphics
Glycolysis
Brain Neoplasms
Cluster Analysis
Adenosine Triphosphatases
Mitochondria
Magnetic Resonance Spectroscopy
Fatty Acids
Biomarkers
Phenotype

Cite this

@conference{82540e4f65554da6a135048492cb7032,
title = "Metabolic heterogeneity among Glioblastoma stem-like cells reflects differences in response to drug treatments.",
abstract = "PurposeGlioblastoma multiforme (GBM) is the most aggressive brain tumor. The cancer stem cell hypothesis postulates the existence within GBM of a small fraction of self-renewing cells with stem like properties (GSCs), resistant to conventional treatments. Metabolic profiling may contribute to discover new diagnostic or prognostic biomarkers to be used for personalized therapies.MethodsForty-four GSC lines, derived from GBM patients were analyzed via MR spectroscopy as described in [1]. Unsupervised Cluster analysis of MR data was performed to identify GSC subgroups with different metabolic profiles. Responses to treatment with oligomycin and etomoxir were examined by MRS and confocal microscopy.ResultsClustering of GSCs evidenced three subgroups: Clusters 1a and 1b, with high intergroup similarity and neural fingerprints, and Cluster 2, with a metabolism typical of commercial tumor lines (Fig. 1) according to [2]. 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 (MRS) and as lipid droplets (confocal microscopy).ConclusionsThese results indicate a relevant role of mitochondrial fatty acids 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.",
author = "Alessandra Palma and Sveva Grande and {Ricci Vitiani}, Lucia and Luciani, {Anna Maria} and Mariachiara Buccarelli and Mauro Biffoni and Agnese Molinari and Annarica Calcabrini and Emanuela D'Amore and Laura Guidoni and Roberto Pallini and Vincenza Viti and Antonella Rosi",
year = "2018",
month = "12",
doi = "https://doi.org/10.1016/j.ejmp.2018.04.316",
language = "English",
pages = "250--251",

}

TY - CONF

T1 - Metabolic heterogeneity among Glioblastoma stem-like cells reflects differences in response to drug treatments.

AU - Palma, Alessandra

AU - Grande, Sveva

AU - Ricci Vitiani, Lucia

AU - Luciani, Anna Maria

AU - Buccarelli, Mariachiara

AU - Biffoni, Mauro

AU - Molinari, Agnese

AU - Calcabrini, Annarica

AU - D'Amore, Emanuela

AU - Guidoni, Laura

AU - Pallini, Roberto

AU - Viti, Vincenza

AU - Rosi, Antonella

PY - 2018/12

Y1 - 2018/12

N2 - PurposeGlioblastoma multiforme (GBM) is the most aggressive brain tumor. The cancer stem cell hypothesis postulates the existence within GBM of a small fraction of self-renewing cells with stem like properties (GSCs), resistant to conventional treatments. Metabolic profiling may contribute to discover new diagnostic or prognostic biomarkers to be used for personalized therapies.MethodsForty-four GSC lines, derived from GBM patients were analyzed via MR spectroscopy as described in [1]. Unsupervised Cluster analysis of MR data was performed to identify GSC subgroups with different metabolic profiles. Responses to treatment with oligomycin and etomoxir were examined by MRS and confocal microscopy.ResultsClustering of GSCs evidenced three subgroups: Clusters 1a and 1b, with high intergroup similarity and neural fingerprints, and Cluster 2, with a metabolism typical of commercial tumor lines (Fig. 1) according to [2]. 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 (MRS) and as lipid droplets (confocal microscopy).ConclusionsThese results indicate a relevant role of mitochondrial fatty acids 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.

AB - PurposeGlioblastoma multiforme (GBM) is the most aggressive brain tumor. The cancer stem cell hypothesis postulates the existence within GBM of a small fraction of self-renewing cells with stem like properties (GSCs), resistant to conventional treatments. Metabolic profiling may contribute to discover new diagnostic or prognostic biomarkers to be used for personalized therapies.MethodsForty-four GSC lines, derived from GBM patients were analyzed via MR spectroscopy as described in [1]. Unsupervised Cluster analysis of MR data was performed to identify GSC subgroups with different metabolic profiles. Responses to treatment with oligomycin and etomoxir were examined by MRS and confocal microscopy.ResultsClustering of GSCs evidenced three subgroups: Clusters 1a and 1b, with high intergroup similarity and neural fingerprints, and Cluster 2, with a metabolism typical of commercial tumor lines (Fig. 1) according to [2]. 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 (MRS) and as lipid droplets (confocal microscopy).ConclusionsThese results indicate a relevant role of mitochondrial fatty acids 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.

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DO - https://doi.org/10.1016/j.ejmp.2018.04.316

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