Tumor cell metabolism

Romero-García, Susana; López‐González, José Sullivan; Báez-Viveros, José Luis; Aguilar-Cázares, Dolores; Prado-Garcı́a, Heriberto

doi:10.4161/cbt.12.11.18140

Cited by 179 publications

(122 citation statements)

References 101 publications

(162 reference statements)

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“…Similarly, demand for glutamine is greater than other nonessential amino acids in cancer cells (Coles and Johnstone, 1962). These alterations are characterized by redistribution of glucose carbons away from catabolism for ATP production toward macromolecule synthesis and maintenance of reductive capacity to sustain proliferation (Romero‐Garcia et al ., 2011). In addition to enhanced glucose and glutamine metabolism, alterations in cancer cell fatty acid (FA) metabolism have been reported (Balaban et al ., 2015).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

et al. 2018

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Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alters MCF‐7 and MDA‐MB‐231 cell metabolism and promotes proliferation and migration. Since adipocytes are FA‐rich, and these FAs are transferred to BrCa cells, we sought to elucidate the FA metabolism of BrCa cells and their response to FA‐rich environments. MCF‐7 and MDA‐MB‐231 cells incubated in serum‐containing media supplemented with FAs accumulate extracellular FAs as intracellular triacylglycerols (TAG) in a dose‐dependent manner, with MDA‐MB‐231 cells accumulating more TAG. The differences in TAG levels were a consequence of distinct differences in intracellular partitioning of FAs, and not due to differences in the rate of FA uptake. Specifically, MCF‐7 cells preferentially partition FAs into mitochondrial oxidation, whereas MDA‐MB‐231 cells partition FAs into TAG synthesis. These differences in intracellular FA handling underpin differences in the sensitivity to palmitate‐induced lipotoxicity, with MDA‐MB‐231 cells being highly sensitive, whereas MCF‐7 cells are partially protected. The attenuation of palmitate‐induced lipotoxicity in MCF‐7 cells was reversed by inhibition of FA oxidation. Pretreatment of MDA‐MB‐231 cells with FAs increased TAG synthesis and reduced palmitate‐induced apoptosis. Our results provide novel insight into the potential influences of obesity on BrCa biology, highlighting distinct differences in FA metabolism in MCF‐7 and MDA‐MB‐231 cells and how lipid‐rich environments modulate these effects.

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Section: Introductionmentioning

confidence: 99%

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

et al. 2018

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“…Tumors contain both aerobic and hypoxic regions that form a metabolic symbiosis that is crucial for tumor cell survival (15,16). The cancer cells located in the hypoxic regions export lactate, which acidifies the tumor environment; the cells located in the aerobic regions, however, import lactate and utilize it for oxidative phosphorylation (4).…”

mentioning

confidence: 99%

2-Methoxyestradiol Reverses the Pro-Carcinogenic Effect of L-Lactate in Osteosarcoma 143B Cells

Górska‐Ponikowska

Kuban–Jankowska

Daca

et al. 2017

CGP

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Abstract. Background Cancer cells are traditionally characterized by increased glucose uptake, high rates of aerobic glycolysis, increased lactic acid production, impaired mitochondrial function and decreased extracellular pH. These characteristics are known as the 'Warburg effect' (1-3). The 'Warburg effect' is also observed in cancer-associated fibroblasts and mesenchymal stem cells (1-11), which secrete lactate and ketones into the microenvironment of the tumor. Lactic acid exists as L-and D-optical isomers. In mammals including humans, lactate is present almost entirely as L-lactate (12, 13). Interestingly, a variety of human cancer cell lines and human tumors, including breast, prostate, head, neck, and osteosarcoma cancers, import these metabolites and deliver them to the mitochondrial TCA cycle, thereby promoting ATP generation and cell proliferation (1-14). According to this 'reverse Warburg effect', tumor cells can induce metabolic reprogramming by shuttling lactate as an energy source to neighboring cancer cells, to the adjacent stroma and to vascular endothelial cells (1,14).Tumors contain both aerobic and hypoxic regions that form a metabolic symbiosis that is crucial for tumor cell survival (15, 16). The cancer cells located in the hypoxic regions export lactate, which acidifies the tumor environment; the cells located in the aerobic regions, however, import lactate and utilize it for oxidative phosphorylation (4). Bonuccelli and colleagues (2) suggested that L-lactate metabolism in cancer cells may explain why diabetic patients have an increased risk of cancer development and a tendency towards autophagy/mitophagy in their adipose tissue. An increased tumor L-lactate level strictly correlates with increased metastasis, tumor recurrence and poor outcome (6-9).L-lactate metabolism and the reverse Warburg effect has been clearly established in osteosarcoma cells. It has been demonstrated that the secretion of lactate and ketones by the mesenchymal stem cells drives mitochondrial biogenesis and increases the mitochondrial activity in osteosarcoma cells (1, 483 This article is freely accessible online.Correspondence to: Magdalena Gorska-Ponikowska (MGP),

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“…Így a tejsav hozzájárul a mitochondrialis mechanizmus felerősítéséhez, a daganatkép-ződéshez és a progresszióhoz [40,41]. Továbbá a tejsav közvetetten elősegíti a hypoxiás daganatsejtek túlélését, amelyek az újonnan képződött erektől távol helyezkednek el [42]. Humán daganatokban -mint glioma, emlő-rák, CRC, gyomor-, méhnyakrák és neuroblastoma -fokozott MCT1-és MCT4-expressziót figyeltek meg, amely rossz prognózissal társult [43][44][45][46].…”

Section: A Tejsav Mint a Daganatsejt Energiaforrásaunclassified

A laktátdehidrogenáz (LDH) prognosztikai jelentősége az onkológiában

Deme¹,

Telekes

2017

Orvosi Hetilap

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A rosszindulatú daganatsejtek többségében fokozott a glikolízis, amely biztosítja a proliferációhoz szükséges energia legnagyobb részét. A laktátdehidrogenáz (LDH) anaerob körülmények között katalizálja a reverzibilis piruvát-tejsav átalakulást. A daganatsejtek által expresszált LDHA izoenzim hatására a tejsavképződés jelentősen fokozódik. A tejsav indukálja az oxigenizált daganatsejtek proliferációját, az angiogenezist és gátolja a veleszületett és az adaptív immunválaszt. A szérum-LDH-emelkedés rövidebb túléléssel korrelál. A szerzők áttekintik az LDH-emelkedés és a rosszindulatú daganatos betegségek prognózisa közötti összefüggést feltáró fontosabb vizsgálatokat. Orv Hetil. 2017; 158(50): 1977-1988. Kulcsszavak: laktátdehidrogenáz, rosszindulatú daganatok, prognózis Prognostic importance of lactate dehydrogenase (LDH) in oncologyGlycolysis is increased in most of the malignant cells, providing the largest proportion of energy needed for cell proliferation. Lactate dehydrogenase (LDH) catalyses the reversible process of pyruvate to lactate in anaerobic condition. LDHA isoenzyme expressed mainly by malignant cells, significantly increases lactate formation. Lactate induces the proliferation of oxygenated malignant cells, angiogenesis, and inhibits the innate and adaptive immune responses. Baseline serum LDH elevation correlates with shorter survival. The authors review the relevant studies exploring the correlation between LDH elevation and the prognosis of malignant diseases. Rövidítések A549 = (human non small cell lung cancer cell line A549) humán nem kissejtes tüdőráksejtvonal A549; acetil-CoA = (acetylcoenzyme A) acetil-koenzim A; Acr = activity-regulated cytoskeleton-associated protein; AKT = (protein kinase B) proteinkináz-B; AMP = (adenosine monophosphate) adenozin-monofoszfát; AMPK = (adenosine monophosphate-activated protein kinase) adenozin-monofoszfát aktiválta proteinkináz; ARG1 = (L-arginin metabolizing enzyme arginase-1) L-arginin-metabolizáló enzim argináz-1; ATP = (adenosine triphosphate) adenozin-trifoszfát; CAF = (cancer-associated fibroblasts) daganat asszociálta fibroblastok; CD = (cluster of differentation) differenciációs cluster; CRC = (colorectal cancer) vastag-és végbélrák; CRPC = (castration-resistant prostate cancer) kasztrációrezisztens prostatarák; CSS = (cancer specific survival) daganatspecifikus túlélés; CTL = (cytotoxic T-lymphocyte) citotoxikus T-lymphocyta; DFS = (disease-free survival) betegségmentes túlélés; EGFR = (epidermal growth factor receptor) epidermális növekedési faktor receptor; EpH4 = (nontumorigenic mammary epithelial cells) nem daganatos emlőhámsejt; ER = (estrogen receptor) ösztrogénreceptor; ErbB2 = receptor tyrosine kinase erbB-2 (HER-2/Neu); ERK-2 = (extracellular signal-regulated kinase-2) extracelluláris szignál regulálta kináz 2; FH = (fumarate hydratase) fumaráthidra-táz; c-Fos = Finkel-Biskis-Jinkins-osteosarcoma; FX11 = kis molekulájú LDHA-inhibitor; G6PDH = (glucose-6-phos- Keywords

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Tumor cell metabolism

Cited by 179 publications

References 101 publications

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

2-Methoxyestradiol Reverses the Pro-Carcinogenic Effect of L-Lactate in Osteosarcoma 143B Cells

A laktátdehidrogenáz (LDH) prognosztikai jelentősége az onkológiában

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