Therapeutic potential of targeting glucose metabolism in glioma stem cells

Nakano, ﻿Ichiro

doi:10.1517/14728222.2014.944899

Cited by 24 publications

(26 citation statements)

References 27 publications

(22 reference statements)

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“…It was found that CSCs can modify their nutrient consumption to survive chronic glucose deprivation . As a mechanistic explanation, it has been shown that stem‐like cells in GBMs can adapt to glucose limitations by co‐opting high affinity glucose transporters thereby increasing the efficiency of glucose uptake .…”

Section: Environmental Stress and Therapeutic Insults Alter Csc Metabmentioning

confidence: 99%

Targeting cancer stem‐like cells in glioblastoma and colorectal cancer through metabolic pathways

Kahlert

Mooney

Natsumeda

et al. 2016

Intl Journal of Cancer

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Cancer stem-like cells (CSCs) are thought to be the main cause of tumor occurrence, progression and therapeutic resistance. Strong research efforts in the last decade have led to the development of several tailored approaches to target CSCs with some very promising clinical trials underway; however, until now no anti-CSC therapy has been approved for clinical use. Given the recent improvement in our understanding of how onco-proteins can manipulate cellular metabolic networks to promote tumorigenesis, cancer metabolism research may well lead to innovative strategies to identify novel regulators and downstream mediators of CSC maintenance. Interfering with distinct stages of CSC-associated metabolics may elucidate novel, more efficient strategies to target this highly malignant cell population. Here recent discoveries regarding the metabolic properties attributed to CSCs in glioblastoma (GBM) and malignant colorectal cancer (CRC) were summarized. The association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks were also discussed. The recent developments in metabolic imaging to identify CSCs were also summarized. This summary should comprehensively update basic and clinical scientists on the metabolic traits of CSCs in GBM and malignant CRC.

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Section: Environmental Stress and Therapeutic Insults Alter Csc Metabmentioning

confidence: 99%

Targeting cancer stem‐like cells in glioblastoma and colorectal cancer through metabolic pathways

Kahlert

Mooney

Natsumeda

et al. 2016

Intl Journal of Cancer

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“…Like normal (non tumor) stem cells, CSCs are characterized by a hyper-glycolytic metabolism (Warburg effect) [26,27], and lowered mitochondrial respiration, compared to more differentiated and committed cells within the tumor bulk [6,28,29] .…”

Section: Glioma Cancer Stem Cells (Cscs): Phenotypic Featuresmentioning

confidence: 99%

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

et al. 2015

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Glioblastoma multiforme (GBM) are extremely lethal and still poorly treated primary brain tumors, characterized by the presence of highly tumorigenic cancer stem cell (CSC) subpopulations, considered responsible for tumor relapse. In order to successfully eradicate GBM growth and recurrence, new anti-cancer strategies selectively targeting CSCs should be designed. CSCs might be eradicated by targeting some of their cell surface markers and transporters, inducing their differentiation, impacting their hyper-glycolytic metabolism, inhibiting CSC-related signaling pathways and/or by targeting their microenvironmental niche. In this regard, phytocompounds such as curcumin, isothiocyanates, resveratrol and epigallocatechin-3-gallate have been shown to prevent or reverse cancer-related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemotherapy and radiotherapy efficacy. However, the actual bioavailability and metabolic processing of phytocompounds is generally unknown, and the presence of the blood brain barrier often represents a limitation to glioma treatments. Nowadays, nanoparticles (NPs) can be loaded with therapeutic compounds such as phytochemicals, improving their bioavailability and their targeted delivery within the GBM tumor bulk. Moreover, NPs can be designed to increase their tropism and specificity toward CSCs by conjugating their surface with antibodies specific for CSC antigens, with ligands or with glucose analogues. Here we discuss the use of phytochemicals as anti-glioma agents and the applicability of phytochemical-loaded NPs as drug delivery systems to target GBM. Additionally, we provide some examples on how NPs can be specifically formulated to improve CSC targeting.

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“…One of the hallmarks of cancer that is of renewed interest is the ability of cells to adapt their metabolism to favor aerobic glycolysis over oxidative phosphorylation, a phenomenon known as the Warburg effect [11]. While the Warburg effect has been observed in glioma [12], it is also known that the metabolism of these brain cancers can be pliable. In vitro, glioblastomas have shown variability in their mitochondrial respiration, while tissue derived GBM cell lines have shown glucose dependency and a reliance on fatty acid oxidation [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The Quiescent Metabolic Phenotype of Glioma Stem Cells

Spehalski¹,

Lee²,

Peters³

et al. 2019

J Proteomics Bioinform

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Introduction: Glioblastoma (GBM) is the most common primary malignant brain tumor in humans and, even with aggressive treatment that includes surgical resection, radiation (IR), and chemotherapy administration, prognosis is poor due to tumor recurrence. There is evidence that within GBMs a small number of glioma stem-like cells (GSLCs) exist, which are thought to be therapy resistant and are thus capable of repopulating a tumor after treatment. Like most cancers, GBMs largely employ aerobic glycolysis to create ATP, a phenomenon known as the Warburg Effect. There is no consensus on the metabolic characteristics of cancer stem cells. GSLCs have been shown to rely more heavily on oxidative phosphorylation, but there is also evidence that cancer stem cells can adapt their metabolism by fluctuating between energy pathways or acquiring intermediate metabolic phenotypes. We hypothesized that the metabolism of GSLCs differs from that of differentiated GBM tumor cell lines, and that the steady state metabolism would be differentially altered following radiation treatment. Materials and Methods: We evaluated the oxygen consumption rate, extracellular acidification rate, and metabolic enzyme levels of GBM cell lines and GSLCs before and after irradiation using extracellular flux assays. We also measured absolute metabolite levels in these cells via mass spectroscopy with and without radiation treatment. Results: GSLCs were found to be significantly more quiescent in comparison to adherent GBM cell lines, highlighted by lower glycolytic and maximal respiratory capacities as well as lower oxygen consumption and extracellular acidification rates. Analysis of individual metabolite concentrations revealed lower total metabolite concentrations overall but also elevated levels of metabolites in different energy pathways for GSLCs compared to GBM cell lines. Additionally, the metabolism of both GSLCs and GBM cell lines were found to be altered by IR. Conclusion: While there is not one metabolic alteration that distinguishes irradiated GSLC metabolism from that of GBM cell lines, therapies targeting more metabolically quiescent tumor cells and thus the resistant GSLC population may increase a cancer's sensitivity to radiotherapy.

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Therapeutic potential of targeting glucose metabolism in glioma stem cells

Cited by 24 publications

References 27 publications

Targeting cancer stem‐like cells in glioblastoma and colorectal cancer through metabolic pathways

Targeting cancer stem‐like cells in glioblastoma and colorectal cancer through metabolic pathways

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

The Quiescent Metabolic Phenotype of Glioma Stem Cells

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