7,488
Views
250
CrossRef citations to date
0
Altmetric
Report

Ketones and lactate increase cancer cell “stemness,” driving recurrence, metastasis and poor clinical outcome in breast cancer

Achieving personalized medicine via Metabolo-Genomics

Pages 1271-1286 | Received 24 Feb 2011, Accepted 02 Mar 2011, Published online: 15 Apr 2011

References

  • Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, et al. The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009; 8:3984 - 4001
  • Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, et al. The Autophagic Tumor Stroma Model of Cancer: Role of Oxidative Stress and Ketone Production in Fueling Tumor Cell Metabolism. Cell Cycle 2010; 9:3485 - 3505
  • Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Loss of Stromal Caveolin-1 Leads to Oxidative Stress, Mimics Hypoxia and Drives Inflammation in the Tumor Microenvironment, Conferring the “Reverse Warburg effect”: A Transcriptional Informatics Analysis with Validation. Cell Cycle 2010; 9:2201 - 2219
  • Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, et al. Oxidative Stress in Cancer Associated Fibroblasts Drives Tumor-Stroma Co-Evolution: A New Paradigm for Understanding Tumor Metabolism, the Field Effect and Genomic Instability in Cancer Cells. Cell Cycle 2010; 9:3256 - 3276
  • Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman JN, et al. Tumor Cells Induce the Cancer Associated Fibroblast Phenotype Via Caveolin-1 Degradation: Implications for Breast Cancer and DCIS Therapy with Autophagy Inhibitors. Cell Cycle 2010; 9:2423 - 2433
  • Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, et al. Autophagy in Cancer Associated Fibroblasts Promotes Tumor Cell Survival: Role of Hypoxia, HIF1 Induction and NFκB Activation in the Tumor Stromal Microenvironment. Cell Cycle 2010; 9:3515 - 3533
  • Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Casey T, et al. The Autophagic Tumor Stroma Model of Cancer or “Battery-Operated Tumor Growth”: A Simple Solution to the Autophagy Paradox. Cell Cycle 2010; 9:4297 - 4306
  • Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, et al. Ketones and Lactate “Fuel” Tumor Growth and Metastasis: Evidence that Epithelial Cancer Cells Use Oxidative Mitochondrial Metabolism. Cell Cycle 2010; 9:3506 - 3514
  • Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, et al. Understanding the “lethal” drivers of tumor-stroma co-evolution: Emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor microenvironment. Cancer Biol Ther 2010; 10:537 - 542
  • Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Tanowitz HB, Sotgia F, Lisanti MP. Stromalepithelial metabolic coupling in cancer: Integrating autophagy and metabolism in the tumor microenvironment. Int J Biochem Cell Biol 2011; In press
  • Gorr TA, Wichmann D, Pilarsky C, Theurillat JP, Fabrizius A, Laufs T, et al. Old proteins—new locations: myoglobin, haemoglobin, neuroglobin and cytoglobin in solid tumours and cancer cells. Acta Physiol (Oxf) 2011; In press
  • Kristiansen G, Rose M, Geisler C, Fritzsche FR, Gerhardt J, Luke C, et al. Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype. Br J Cancer 2010; 102:1736 - 1745
  • Moreaux J, Cremer FW, Reme T, Raab M, Mahtouk K, Kaukel P, et al. The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature. Blood 2005; 106:1021 - 1030
  • Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, Mueller-Klieser W. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001; 51:349 - 353
  • Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK, Mueller-Klieser W. High lactate levels predict likelihood of metastases, tumor recurrence and restricted patient survival in human cervical cancers. Cancer Res 2000; 60:916 - 921
  • Walenta S, Mueller-Klieser WF. Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol 2004; 14:267 - 274
  • Walenta S, Salameh A, Lyng H, Evensen JF, Mitze M, Rofstad EK, Mueller-Klieser W. Correlation of high lactate levels in head and neck tumors with incidence of metastasis. Am J Pathol 1997; 150:409 - 415
  • Sculier JP, Nicaise C, Klastersky J. Lactic acidosis: a metabolic complication of extensive metastatic cancer. Eur J Cancer Clin Oncol 1983; 19:597 - 601
  • Varanasi UR, Carr B, Simpson DP. Lactic acidosis associated with metastatic breast carcinoma. Cancer Treat Rep 1980; 64:1283 - 1285
  • McConnell AA, Parfitt VL, Walker PR. An unusual case of shock in a young woman. Postgrad Med J 1989; 65:120
  • Warner E. Type B lactic acidosis and metastatic breast cancer. Breast Cancer Res Treat 1992; 24:75 - 79
  • Evans TR, Stein RC, Ford HT, Gazet JC, Chamberlain GV, Coombes RC. Lactic acidosis. A presentation of metastatic breast cancer arising in pregnancy. Cancer 1992; 69:453 - 456
  • Cheng JC, Esparza SD, Knez VM, Sakamoto KM, Moore TB. Severe lactic acidosis in a 14-year-old female with metastatic undifferentiated carcinoma of unknown primary. J Pediatr Hematol Oncol 2004; 26:780 - 782
  • Xu HN, Nioka S, Glickson JD, Chance B, Li LZ. Quantitative mitochondrial redox imaging of breast cancer metastatic potential. J Biomed Opt 2010; 15:36010
  • Chen V, Shtivelman E. CC3/TIP30 regulates metabolic adaptation of tumor cells to glucose limitation. Cell Cycle 2010; 9:4941 - 4953
  • Chen EI, Hewel J, Krueger JS, Tiraby C, Weber MR, Kralli A, et al. Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res 2007; 67:1472 - 1486
  • Magistretti PJ. Neuron-glia metabolic coupling and plasticity. J Exp Biol 2006; 209:2304 - 2311
  • Magistretti PJ. Role of glutamate in neuron-glia metabolic coupling. Am J Clin Nutr 2009; 90:875 - 880
  • Magistretti PJ, Pellerin L. The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation studies. Mol Psychiatry 1996; 1:445 - 452
  • Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Transcriptional evidence for the “Reverse Warburg effect” in human breast cancer tumor stroma and metastasis: similarities with oxidative stress, inflammation, Alzheimer's disease, and “Neuron-Glia Metabolic Coupling”. Aging (Albany NY) 2010; 2:185 - 199
  • Wohnsland S, Burgers HF, Kuschinsky W, Maurer MH. Neurons and neuronal stem cells survive in glucose-free lactate and in high glucose cell culture medium during normoxia and anoxia. Neurochem Res 2010; 35:1635 - 1642
  • Birket MJ, Orr AL, Gerencser AA, Madden DT, Vitelli C, Swistowski A, et al. A reduction in ATP demand and mitochondrial activity with neural differentiation of human embryonic stem cells. J Cell Sci 2010; 124:348 - 358
  • Harvey A, Gibson T, Lonergan T, Brenner C. Dynamic regulation of mitochondrial function in preimplantation embryos and embryonic stem cells. Mitochondrion 2011; In press
  • Markowetz F, Mulder KW, Airoldi EM, Lemischka IR, Troyanskaya OG. Mapping dynamic histone acetylation patterns to gene expression in nanog-depleted murine embryonic stem cells. PLoS Comput Biol 2010; 6:1001034
  • Fenselau A, Wallis K, Morris HP. Subcellular localization of acetoacetate coenzyme A transferase in rat hepatomas. Cancer Res 1976; 36:4429 - 4433
  • Kallinowskil F, Davel S, Vaupell P, Baessler KH, Wagner K. Glucose, lactate and ketone body utilization by human mammary carcinomas in vivo. Adv Exp Med Biol 1985; 191:763 - 773
  • Authier S, Tremblay S, Dumulon V, Dubuc C, Ouellet R, Lecomte R, et al. [11C] acetoacetate utilization by breast and prostate tumors: a PET and biodistribution study in mice. Mol Imaging Biol 2008; 10:217 - 223
  • Prenen GH, Go KG, Zuiderveen F, Paans AM, Vaalburg W. An improved synthesis of carbon-11 labeled acetoacetic acid and an evaluation of its potential for the investigation of cerebral pathology by positron emission tomography. Int J Rad Appl Instrum A 1990; 41:1209 - 1216
  • Dykens JA, Jamieson J, Marroquin L, Nadanaciva S, Billis PA, Will Y. Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro. Toxicol Appl Pharmacol 2008; 233:203 - 210
  • Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila) 2010; 3:1060 - 1065
  • Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformin prevents tobacco carcinogen-induced lung tumorigenesis. Cancer Prev Res (Phila) 2010; 3:1066 - 1076
  • Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res 2009; 69:7507 - 7511
  • Vazquez-Martin A, Oliveras-Ferraros C, Barco SD, Martin-Castillo B, Menendez JA. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat 2011; 126:355 - 364
  • Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Martin-Castillo B, Menendez JA. Metformin and energy metabolism in breast cancer: from insulin physiology to tumour-initiating stem cells. Curr Mol Med 2010; 10:674 - 691
  • Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Del Barco S, Martin-Castillo B, Menendez JA. Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle 2010; 9:3807 - 3814
  • Biradar V, Moran JL, Peake SL, Peter JV. Metformin-associated lactic acidosis (MALA): clinical profile and outcomes in patients admitted to the intensive care unit. Crit Care Resusc 2010; 12:191 - 195
  • Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102:15545 - 15550
  • Barrett T, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista C, et al. NCBI GEO: mining tens of millions of expression profiles—database and tools update. Nucl Acids Res 2007; 35:760 - 765
  • Brazma A, Parkinson H, Sarkans U, Shojatalab M, Vilo J, Abeygunawardena N, et al. ArrayExpress—a public repository for microarray gene expression data at the EBI. Nucleic Acids Res 2003; 31:68 - 71
  • Ertel A. Bimodal gene expression and biomarker discovery. Cancer Inform 2010; 9:11 - 14
  • Ertel A, Dean JL, Rui H, Liu C, Witkiewicz AK, Knudsen KE, Knudsen ES. RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeutic response. Cell Cycle 2010; 9:4153 - 4163
  • Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006; 7:96