Role of Lactic Acid in Cancer Metabolism Under the Influences on Tumor Expansion and Metamorphosis: A Review
Science Journal of Clinical Medicine
Volume 9, Issue 1, March 2020, Pages: 1-6
Received: Dec. 24, 2019;
Accepted: Jan. 2, 2020;
Published: Jan. 10, 2020
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Sameer Sharma, Department of Biotechnology, Indian Academy Degree College-Autonomous, Bangalore, India
Rajan Chourasiya, Department of Biotechnology, Indian Academy Degree College-Autonomous, Bangalore, India
Shahna T, Department of Biotechnology, Indian Academy Degree College-Autonomous, Bangalore, India
Gaddam Roopa Shivani, Department of Biotechnology, Indian Academy Degree College-Autonomous, Bangalore, India
Anaerobic glycolysis advertise the production of energy under hypoxic condition (absence of oxygen), while in aerobic glycolysis, the Warburg effect gives a momentous benefit through remodeling carbohydrates seeds from production of energy to biochemical pathways. On the other side, high degree of lactate have been cooperated with feeble outcome in human tumors as well as glycolytic switch is correlated with high rate of glucose uptake and lactate production. Although lactic acid was primarily remind as indicator of the glycolytic process in which many mechanisms initiates from the study of normal tissue physiology and transported to the tumor indicating lactic acid in essence lactate anion and protons, straightly contributes to tumor growth and development. MCT1 & MCT4 monocarboxylate transporters have been justified as well-known facilitators of lactate exchanges between various cancer cells with many metabolic behaviors. In this review, we summarize the current knowledge on the role of lactic acidosis and metastasis, lactate shuttles and lactate signaling molecules.
Gaddam Roopa Shivani,
Role of Lactic Acid in Cancer Metabolism Under the Influences on Tumor Expansion and Metamorphosis: A Review, Science Journal of Clinical Medicine.
Vol. 9, No. 1,
2020, pp. 1-6.
Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006; 3: 177-85.
Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006; 3: 187-97.
DeBerardinis RJ, Mancuso A, Daikhin E, et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 2007; 104: 19345-50.
Dimmer KS, Friedrich B, Lang F, Deitmer JW, Broer S. The lowaffinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J 2000; 350 Pt 1: 219-27.
Walenta S, Mueller-Klieser WF. Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol 2004; 14: 267-74.
Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol 1927; 8: 519-30.
Gambhir SS, Czernin J, Schwimmer J, Silverman DH, Coleman RE, Phelps ME. A tabulated summary of the FDG PET literature. J Nucl Med 2001; 42: 1S-93S.
Kelloff GJ, Hoffman JM, Johnson B, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 2005; 11: 2785-808.
Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol 2004; 558: 5-30.
Cori CF, Cori GT. Glycogen formation in the liver with d- and llactic acid. J Biol Chem 1929; 81: 389-403.
Sonveaux P, Vegran F, Schroeder T, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 2008; 118: 3930-42.
Semenza GL. Tumor metabolism: cancer cells give and take lactate. J Clin Invest 2008; 118: 3835-7.
Feron O. Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiother Oncol 2009; 92: 329-33.
Bonuccelli G, Tsirigos A, Whitaker-Menezes D, et al. Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 2010; 9: 3506-14.
Martinez-Outschoorn UE, Pavlides S, Howell A, et al. Stromalepithelial metabolic coupling in cancer: Integrating autophagy and metabolism in the tumor microenvironment. Int J Biochem Cell Biol 2011; 43: 1045-51.
Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, et al. Evidence for a stromal-epithelial "lactate shuttle" in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle 2011; 10: 1772-83.
Lu H, Forbes RA, Verma A. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem 2002; 277: 23111-5.
Lu H, Dalgard CL, Mohyeldin A, McFate T, Tait AS, Verma A. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J Biol Chem 2005; 280: 41928-39.
Vegran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-kappaB/IL-8 pathway that drives tumor angiogenesis. Cancer Res 2011; 71: 2550-60.
Gallagher SM, Castorino JJ, Wang D, Philp NJ. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDAMB-231. Cancer Res 2007; 67: 4182-9.
Deora AA, Philp N, Hu J, Bok D, Rodriguez-Boulan E. Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia. Proc Natl Acad Sci USA 2005; 102: 16245-50
Slomiany MG, Grass GD, Robertson AD, et al. Hyaluronan, CD44, and emmprin regulate lactate efflux and membrane localization of monocarboxylate transporters in human breast carcinoma cells. Cancer Res 2009; 69: 1293-301.
Ellis SM, Nabeshima K, Biswas C. Monoclonal antibody preparation and purification of a tumor cell collagenase-stimulatory factor. Cancer Res 1989; 49: 3385-91.
Ishibashi Y, Matsumoto T, Niwa M, et al. CD147 and matrix metalloproteinase-2 protein expression as significant prognostic factors in esophageal squamous cell carcinoma. Cancer 2004; 101: 1994-2000.
Ueda K, Yamada K, Urashima M, et al. Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3. Oncol Rep 2007; 17: 731-5.
Biswas C, Zhang Y, DeCastro R, et al. The human tumor cellderived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res 1995; 55: 434-9.
Kanekura T, Chen X, Kanzaki T. Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer 2002; 99: 520-8.
Chen X, Lin J, Kanekura T, et al. A small interfering CD147- targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma. Cancer Res 2006; 66: 11323- 30.
Miyauchi S, Gopal E, Fei YJ, Ganapathy V. Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. J Biol Chem 2004; 279: 13293-6.
Gopal E, Fei YJ, Sugawara M, et al. Expression of slc5a8 in kidney and its role in Na(+)-coupled transport of lactate. J Biol Chem 2004; 279: 44522-32.
Ganapathy V, Thangaraju M, Gopal E, et al. Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. AAPS J 2008; 10: 193-9.
Li H, Myeroff L, Smiraglia D, et al. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci USA 2003; 100: 8412-7.
Bonen A. The expression of lactate transporters (MCT1 and MCT4) in heart and muscle. Eur J Appl Physiol 2001; 86: 6-11.
McCullagh KJ, Poole RC, Halestrap AP, O'Brien M, Bonen A. Role of the lactate transporter (MCT1) in skeletal muscles. Am J Physiol 1996; 271: E143-50.
Bonen A, McCullagh KJ, Putman CT, Hultman E, Jones NL, Heigenhauser GJ. Short-term training increases human muscle MCT1 and femoral venous lactate in relation to muscle lactate. Am J Physiol 1998; 274: E102-7.
Bouzier-Sore AK, Voisin P, Canioni P, Magistretti PJ, Pellerin L. Lactate is a preferential oxidative energy substrate over glucose for neurons in culture. J Cereb Blood Flow Metab 2003; 23: 1298-306.
Pellerin L, Magistretti PJ. Neuroenergetics: calling upon astrocytes to satisfy hungry neurons. Neuroscientist 2004; 10: 53-62.
Pellerin L, Bergersen LH, Halestrap AP, Pierre K. Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. J Neurosci Res 2005; 79: 55-64.
Halestrap AP, Meredith D. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 2004; 447: 619-28.
Curi R, Newsholme P, Newsholme EA. Metabolism of pyruvate by isolated rat mesenteric lymphocytes, lymphocyte mitochondria and isolated mouse macrophages. Biochem J 1988; 250: 383-8.
Chiche J, Fur YL, Vilmen C, et al. In vivo pH in metabolicdefective Ras-transformed fibroblast tumors: Key role of the monocarboxylate transporter, MCT4, for inducing an alkaline intracellular pH. Int J Cancer 2011.
Ullah MS, Davies AJ, Halestrap AP. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem 2006; 281: 9030-7.
Porporato PE, Dadhich RK, Dhup S, Copetti T, Sonveaux P. Anticancer targets in the glycolytic metabolism of tumors: a comprehensive review. Front Pharmacol 2011; 2: 49.
Newell K, Franchi A, Pouyssegur J, Tannock I. Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity. Proc Natl Acad Sci USA 1993; 90: 1127-31.
Yamagata M, Hasuda K, Stamato T, Tannock IF. The contribution of lactic acid to acidification of tumours: studies of variant cells lacking lactate dehydrogenase. Br J Cancer 1998; 77: 1726-31.
Cardone RA, Casavola V, Reshkin SJ. The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat Rev Cancer 2005; 5: 786-95.
Gatenby RA, Gawlinski ET, Gmitro AF, Kaylor B, Gillies RJ. Acid-mediated tumor invasion: a multidisciplinary study. Cancer Res 2006; 66: 5216-23.
Williams AC, Collard TJ, Paraskeva C. An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis. Oncogene 1999; 18: 3199-204.
Smallbone K, Gatenby RA, Gillies RJ, Maini PK, Gavaghan DJ. Metabolic changes during carcinogenesis: potential impact on invasiveness. J Theor Biol 2007; 244: 703-13.
Izumi H, Takahashi M, Uramoto H, et al. Monocarboxylate transporters 1 and 4 are involved in the invasion activity of human lung cancer cells. Cancer Sci 2011; 102: 1007-13.
Stern R, Shuster S, Neudecker BA, Formby B. Lactate stimulates fibroblast expression of hyaluronan and CD44: the Warburg effect revisited. Exp Cell Res 2002; 276: 24-31.
Rudrabhatla SR, Mahaffey CL, Mummert ME. Tumor microenvironment modulates hyaluronan expression: the lactate effect. J Invest Dermatol 2006; 126: 1378-87.
Hashimoto T, Hussien R, Oommen S, Gohil K, Brooks GA. Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. FASEB J 2007; 21: 2602-12.
Hirsila M, Koivunen P, Gunzler V, Kivirikko KI, Myllyharju J. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J Biol Chem 2003; 278: 30772-80.
Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003; 9: 677-84.
Samuvel DJ, Sundararaj KP, Nareika A, Lopes-Virella MF, Huang Y. Lactate boosts TLR4 signaling and NF-kappaB pathwaymediated gene transcription in macrophages via monocarboxylate transporters and MD-2 up-regulation. J Immunol 2009; 182: 2476-84.
Baumann F, Leukel P, Doerfelt A, et al. Lactate promotes glioma migration by TGF-beta2-dependent regulation of matrix metalloproteinase-2. Neuro Oncol 2009; 11: 368-80.
Shime H, Yabu M, Akazawa T, et al. Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J Immunol 2008; 180: 7175-83.