Cancer metabolism: New insights into classic characteristics

Kato, Yukio; Maeda, Toshio; Suzuki, Atsushi; Baba, Yoshifumi

doi:10.1016/j.jdsr.2017.08.003

Cited by 98 publications

(85 citation statements)

References 182 publications

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“…Extracellular pH (pH e ) becomes acidic due to excess cellular glycolysis. In the presence of oxygen, lactic acid is the main cause of extracellular acidification, a process called the "Warburg effect" or "aerobic glycolysis" [1]. Because the expression of most glycolytic enzymes is driven by hypoxia inducible factor-1 (HIF-1), extracellular acidification is closely related to hypoxia [1].…”

Section: Introductionmentioning

confidence: 99%

“…In the presence of oxygen, lactic acid is the main cause of extracellular acidification, a process called the "Warburg effect" or "aerobic glycolysis" [1]. Because the expression of most glycolytic enzymes is driven by hypoxia inducible factor-1 (HIF-1), extracellular acidification is closely related to hypoxia [1]. Among lactate anion/ H + symporters, also known as monocarboxylate transporters (MCTs), the hypoxia-inducible subtype MCT4 is primarily responsible for the secretion of lactic acid.…”

Section: Introductionmentioning

confidence: 99%

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Adaptation to chronic acidic extracellular pH elicits a sustained increase in lung cancer cell invasion and metastasis

Sutoo

Maeda

Suzuki

et al. 2019

Clin Exp Metastasis

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Acidic extracellular pH (pH e) is an important microenvironment for cancer cells. This study assessed whether adaptation to acidic pH e enhances the metastatic phenotype of tumor cells. The low metastatic variant of Lewis lung carcinoma (LLCm1) cells were subjected to stepwise acidification, establishing acidic pH e-adapted (LLCm1A) cells growing exponentially at pH 6.2. These LLCm1A cells showed increased production of matrix metalloproteinases (MMPs), including MMP-2,-3,-9, and-13, and pulmonary metastasis following injection into mouse tail veins. Although LLCm1A cells exhibited a fibroblastic shape, keratin-5 expression was increased and α-smooth muscle actin expression was reduced. Despite serial passage of these cells at pH 7.4, high invasive activity through Matrigel ® was sustained for at least 28 generations. Thus, adaptation to acidic pH e resulted in a more invasive phenotype, which was sustained during passage at pH 7.4, suggesting that an acidic microenvironment at the primary tumor site is important in the acquisition of a metastatic phenotype.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adaptation to chronic acidic extracellular pH elicits a sustained increase in lung cancer cell invasion and metastasis

Sutoo

Maeda

Suzuki

et al. 2019

Clin Exp Metastasis

Self Cite

View full text Add to dashboard Cite

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“…Aerobic glycolysis, or the Warburg effect, is a hallmark of cancer. 40 The Warburg effect describes the increased use of glycolysis rather than OXPHOS by tumor cells in physiological oxygen conditions (reviewed in Bhattacharya et al). 41 Although OXPHOS produces larger amounts of ATP, it is slower to respond to changing conditions, whereas glycolysis can respond quickly.…”

Section: Metabolic Changes (Glycolysis Lipid Metabolism Mitochondrimentioning

confidence: 99%

Crab Ash Extract has Anti-Proliferative Effects on SK-MEL-28 Melanoma Cells and Induces a Cellular Stress Response and Metabolic Changes

Katran¹,

Brestovac²,

Dye³

2019

TJNPR

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There is very limited published data describing medicinal uses of Portunus extract. A recent report describes the identification of a glycosaminoglycan extracted from Portunus pelagicus as an inhibitor of β-secretase 1 (BACE), which plays a role in the pathogenesis of Alzheimer's Disease. 11 However, to our knowledge, there are no publications describing anti-cancer properties of Portunus extract. Data from the International Agency for Research on Cancer indicates there were 17 million new cases of cancer worldwide in 2018, with this projected to increase to 27.5 million new cases per year by 2040, if recent trends continue. 12 The most common cancers in 2018 were breast, prostate, lung and colorectal. Cutaneous melanoma was the 19th most common cancer worldwide in 2018 but shows significant variation in incidence rates across ethnic groups, with fair skinned people the most affected. 13 Melanoma is also one of the most common cancers in young adults and as such, is responsible for many years of life lost per death. Australia and New Zealand have the highest incidence of melanoma with 15,229 new diagnosed cases predicted in 2019. 14 Until 2011, the main treatment of metastatic melanoma was dacarbazine, which showed limited efficacy. 15 Since then, the Food and Drug administration (FDA) has approved immunotherapies, targeted therapies and an oncolytic virus for treatment of melanoma. 16 However, these therapies can have significant side effects, and in the case of targeted therapies (such as BRAF inhibitors), patients often acquire resistance within months, limiting their clinical use. 16 Thus, the identification and development of new therapeutic options for melanoma remains a priority. In this study, the melanoma cell line SK-MEL-28 cell line was treated with Portunus extracts, derived from whole crab ash (CA), shell, and muscle fibers, at different concentrations. CA ethanol extract had the greatest effect on cell proliferation, with 50% cell death after 24 hours at 1250 µg/mL. SK-MEL-28 cells were then treated with a sub-lethal concentration of CA ethanol extract (750 µg/mL, 24 hours) and cell lysates subjected to proteome analysis. Compared to control cells, cells

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“…In hypoxic environments, these cells produce large quantities of lactic acid by anaerobic glycolysis. Conversely, in aerobic conditions, tumor cells rely on glycolysis for energy production (18), resulting in elevated rates of glucose uptake and increase lactate production (19). Lactate production during active tumor growth alters the tumor microenvironment (TME) by promoting acidosis, serving as a metabolic cancer cell fuel source, and inducing immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

Radiation Induced Metabolic Alterations Associate with Tumor Aggressiveness and Poor Outcome in Glioblastoma

Gupta

Vučković

Zhang

et al. 2020

Preprint

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AbstractGlioblastoma (GBM) is uniformly fatal with a one year median survival rate, despite the best available treatment, including radiotherapy (RT). Impacts of prior RT on tumor recurrence are poorly understood but may increase tumor aggressiveness. Metabolic changes have been investigated in radiation-induced brain injury; however, the tumor-promoting effect following prior radiation is lacking. Since RT is vital to GBM management, we quantified the tumor-promoting effects of prior radiotherapy (RT) on patient-derived intracranial GBM xenografts and characterized the metabolic alterations associated with the protumorigenic microenvironment. Human xenografts (GBM143) were implanted into nude mice 24h following 20Gy cranial radiation vs. sham animals. Tumors in pre-radiated mice were more proliferative and more infiltrative, yielding faster mortality (p<0.0001). Histologic evaluation of tumor associated macrophage/microglia (TAMs) revealed cells with a more fully activated ameboid morphology in pre-radiated animals. Microdialyzates from the radiated brain at the margin of tumor infiltration contralateral to the site of implantation were analyzed by unsupervised liquid chromatography-mass spectrometry (LC-MS). In pre-radiated animals, metabolites known to be associated with tumor progression (like, modified nucleotides and polyols) were identified. Whole-tissue metabolomic analysis of the pre-radiated brain microenvironment for metabolic alterations in a separate cohort of nude mice using 1H-NMR revealed significant decrease in levels of antioxidants (glutathione (GSH) and ascorbate (ASC)), NAD+, TCA intermediates, and increased ATP and GTP. Glutathione and ASC showed highest VIPpred (1.65) in OPLS-DA analysis. Involvement of ASC catabolism was further confirmed by GC-MS. To assess longevity of radiation effects, we compared survival with implantation occuring 2 months vs. 24h following radiation, finding worse survival in animals implanted at 2 months. These radiation-induced alterations are consistent with a chronic disease-like microenvironment characterized by reduced levels of antioxidants and NAD+, as well as elevated extracellular ATP and GTP serving as chemoattractants, promoting cell motility and vesicular secretion with decreased levels of GSH and ASC exacerbating oxidative stress. Taken together, these data suggest that IR induces tumor-permissive changes in the microenvironment with metabolomic alterations that may facilitate tumor aggressiveness with important implications for recurrent glioblastoma. Harnessing these metabolomic insights may provide opportunities to attenuate RT-associated aggressiveness of recurrent GBM.

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Cancer metabolism: New insights into classic characteristics

Cited by 98 publications

References 182 publications

Adaptation to chronic acidic extracellular pH elicits a sustained increase in lung cancer cell invasion and metastasis

Adaptation to chronic acidic extracellular pH elicits a sustained increase in lung cancer cell invasion and metastasis

Crab Ash Extract has Anti-Proliferative Effects on SK-MEL-28 Melanoma Cells and Induces a Cellular Stress Response and Metabolic Changes

Radiation Induced Metabolic Alterations Associate with Tumor Aggressiveness and Poor Outcome in Glioblastoma

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