Lactate transporters in the context of prostate cancer metabolism: What do we know?

International Journal of Molecular Sciences

Volumn 15, Issue 10, 2014, Pages 18333-18348

  Pértega Gomes, Nelma ^a,b   Baltazar, Fátima ^a,b  

^a UNIVERSITY OF MINHO   (Portugal)

^b UNIVERSITY OF MINHO   (Portugal)

Author keywords

Cancer metabolism; Monocarboxylate transporters; Prostate cancer; Therapeutic targets

Indexed keywords

4,4 O DIISOTHIOCYANOSTILBENE 2,2 DISULPHONATE; 4,4' DIBENZAMIDOSTILBENE 2,2' DISULFONATE; ALPHA CYANO 4 HYDROXYCINNAMIC ACID; ANTINEOPLASTIC AGENT; AR C155858; BIOFLAVONOID; BIOLOGICAL MARKER; CD147 ANTIGEN; FLUORODEOXYGLUCOSE F 18; LACTIC ACID; MONOCARBOXYLATE TRANSPORTER; MONOCARBOXYLATE TRANSPORTER 1; MONOCARBOXYLATE TRANSPORTER 2; MONOCARBOXYLATE TRANSPORTER 4; PHLORETIN; QUERCETIN; UNCLASSIFIED DRUG;

ANTIGEN EXPRESSION; CANCER CELL; CANCER DIAGNOSIS; CANCER GROWTH; CANCER PROGNOSIS; CANCER THERAPY; CELL METABOLISM; DIAGNOSTIC VALUE; DRUG TARGETING; ENERGY METABOLISM; FIBROBLAST; GLYCOLYSIS; HUMAN; NONHUMAN; PROSTATE CANCER; PROSTATE CARCINOMA; REVIEW; TUMOR MICROENVIRONMENT; ANIMAL; MALE; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOLOGY; PROSTATE; PROSTATIC NEOPLASMS;

ANIMALS; ENERGY METABOLISM; GLYCOLYSIS; HUMANS; LACTIC ACID; MALE; MOLECULAR TARGETED THERAPY; MONOCARBOXYLIC ACID TRANSPORTERS; PROSTATE; PROSTATIC NEOPLASMS; TUMOR MICROENVIRONMENT;

EID: 84907833339     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms151018333     Document Type: Review

References (79)

1. Siegel, R.; Ward, E.; Brawley, O.; Jemal, A. Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA: A Cancer J. Clin. 2011, 61, 212-236.
2. American Cancer Society. Cancer Facts & Figures 2010; American Cancer Society Inc.: Atlanta, GA, USA, 2010.
3. Hsing, A. W.; Tsao, L.; Devesa, S. S. International trends and patterns of prostate cancer incidence and mortality. Int. J. Cancer 2000, 85, 60-67.
4. Potosky, A. L.; Kessler, L.; Gridley, G.; Brown, C. C.; Horm, J. W. Rise in prostatic cancer incidence associated with increased use of transurethral resection. J. Natl. Cancer Inst. 1990, 82, 1624-1628.
5. Delongchamps, N. B.; Singh, A.; Haas, G. P. The role of prevalence in the diagnosis of prostate cancer. Cancer Control 2006, 13, 158-168.
6. Welch, H. G.; Albertsen, P. C. Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986-2005. J. Natl. Cancer Inst. 2009, 101, 1325-1329.
7. Boyle, P.; Maisonneuve, P.; Napalkov, P. Geographical and temporal patterns of incidence and mortality from prostate cancer. Urology 1995, 46, 47-55.
8. Hanahan, D.; Weinberg, R. A. The hallmarks of cancer. Cell 2000, 100, 57-70.
9. Hanahan, D.; Weinberg, R. A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646-674.
10. Warburg, O. On the origin of cancer cells. Science 1956, 123, 309-314.
11. De Berardinis, R. J.; Lum, J. J.; Hatzivassiliou, G.; Thompson, C. B. The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008, 7, 11-20.
12. Jones, R. G.; Thompson, C. B. Tumor suppressors and cell metabolism: A recipe for cancer growth. Genes Dev. 2009, 23, 537-548.
13. Hsu, P. P.; Sabatini, D. M. Cancer cell metabolism: Warburg and beyond. Cell 2008, 134, 703-707.
14. Phelps, M. E. PET: The merging of biology and imaging into molecular imaging. J. Nucl. Med. 2000, 41, 661-681.
15. Ganapathy, V.; Thangaraju, M.; Prasad, P. D. Nutrient transporters in cancer: Relevance to Warburg hypothesis and beyond. Pharmacol. Ther. 2009, 121, 29-40.
16. Kroemer, G.; Pouyssegur, J. Tumor cell metabolism: Cancer's Achilles' heel. Cancer Cell. 2008, 13, 472-482.
17. Ertel, A.; Tsirigos, A.; Whitaker-Menezes, D.; Birbe, R. C.; Pavlides, S.; Martinez-Outschoorn, U. E.; Pestell, R. G.; Howell, A.; Sotgia, F.; Lisanti, M. P. Is cancer a metabolic rebellion against host aging? In the quest for immortality, tumor cells try to save themselves by boosting mitochondrial metabolism. Cell Cycle 2012, 11, 253-263.
18. Dakubo, G. D.; Parr, R. L.; Costello, L. C.; Franklin, R. B.; Thayer, R. E. Altered metabolism and mitochondrial genome in prostate cancer. J. Clin. Pathol. 2006, 59, 10-16.
19. Costello, L. C.; Franklin, R. B.; Feng, P. Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer. Mitochondrion 2005, 5, 143-153.
20. Costello, L. C.; Liu, Y.; Franklin, R. B.; Kennedy, M. C. Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. J. Biol. Chem. 1997, 272, 28875-28881.
21. Liu, Y.; Costello, L. C.; Franklin, R. B. Prolactin specifically regulates citrate oxidation and m-aconitase of rat prostate epithelial cells. Metabolism 1996, 45, 442-449.
22. Cooper, J. F.; Farid, I. The role of citric acid in the physiology of the prostate. 3. lactate/citrate ratios in benign and malignant prostatic homogenates as an index of prostatic malignancy. J. Urol. 1964, 92, 533-536.
23. Costello, L. C.; Franklin, R. B. The intermediary metabolism of the prostate: A key to understanding the pathogenesis and progression of prostate malignancy. Oncology 2000, 59, 269-282.
24. Costello, L. C.; Feng, P.; Milon, B.; Tan, M.; Franklin, R. B. Role of zinc in the pathogenesis and treatment of prostate cancer: Critical issues to resolve. Prostate Cancer Prostatic Dis. 2004, 7, 111-117.
25. 3) spatial resolution. Radiology 1996, 198, 795-805.
26. Zha, S.; Ferdinandusse, S.; Hicks, J. L.; Denis, S.; Dunn, T. A.; Wanders, R. J.; Luo, J.; de Marzo, A. M.; Isaacs, W. B. Peroxisomal branched chain fatty acid β-oxidation pathway is up-regulated in prostate cancer. Prostate 2005, 63, 316-323.
27. Liu, Y.; Zuckier, L. S.; Ghesani, N. V. Dominant uptake of fatty acid over glucose by prostate cells: A potential new diagnostic and therapeutic approach. Anticancer Res. 2010, 30, 369-374.
28. Quennet, V.; Yaromina, A.; Zips, D.; Rosner, A.; Walenta, S.; Baumann, M. Tumor lactate content predicts for response to fractionated irradiation of human squamous cell carcinomas in nude mice. Radiother. Oncol. 2006, 81, 130-135.
29. Brizel, D. M.; Schroeder, T.; Scher, R. L.; Walenta, S.; Clough, R. W.; Dewhirst, M. 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.
30. Paschen, W.; Djuricic, B.; Mies, G.; Schmidt-Kastner, R.; Linn, F. Lactate and pH in the brain: Association and dissociation in different pathophysiological states. J. Neurochem. 1987, 48, 154-159.
31. Juel, C.; Halestrap, A. P. Lactate transport in skeletal muscle-Role and regulation of the monocarboxylate transporter. J. Physiol. 1999, 517, 633-642.
32. Halestrap, A. P.; Denton, R. M. Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by α-cyano-4-hydroxycinnamate. Biochem. J. 1974, 138, 313-316.
33. Carpenter, L.; Poole, R. C.; Halestrap, A. P. Cloning and sequencing of the monocarboxylate transporter from mouse Ehrlich Lettre tumour cell confirms its identity as MCT1 and demonstrates that glycosylation is not required for MCT1 function. Biochim. Biophys. Acta 1996, 1279, 157-163.
34. Halestrap, A. P.; Price, N. T. The proton-linked monocarboxylate transporter (MCT) family: Structure, function and regulation. Biochem. J. 1999, 343, 281-299.
35. Juel, C. Lactate-proton cotransport in skeletal muscle. Physiol. Rev. 1997, 77, 321-358.
36. Halestrap, A. P.; Meredith, D. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch. 2004, 447, 619-628.
37. Price, N. T.; Jackson, V. N.; Halestrap, A. P. Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past. Biochem. J. 1998, 329, 321-328.
38. Yoon, H.; Fanelli, A.; Grollman, E. F.; Philp, N. J. Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment epithelium. Biochem. Biophys. Res. Commun. 1997, 234, 90-94.
39. Yoon, H.; Philp, N. J. Genomic structure and developmental expression of the chicken nonocarboxylate transporter MCT3 gene. Exp. Eye Res. 1998, 67, 417-424.
40. Garcia, C. K.; Brown, M. S.; Pathak, R. K.; Goldstein, J. L. cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. J. Biol. Chem. 1995, 270, 1843-1849.
41. Jackson, V. N.; Price, N. T.; Carpenter, L.; Halestrap, A. P. Cloning of the monocarboxylate transporter isoform MCT2 from rat testis provides evidence that expression in tissues is species-specific and may involve post-transcriptional regulation. Biochem. J. 1997, 324, 447-453.
42. Dimmer, K. S.; Friedrich, B.; Lang, F.; Deitmer, J. W.; Broer, S. The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem. J. 2000, 350, 219-227.
43. Manning Fox, J. E.; Meredith, D.; Halestrap, A. P. Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J. Physiol. 2000, 529, 285-293.
44. Zhang, F.; Vannucci, S. J.; Philp, N. J.; Simpson, I. A. Monocarboxylate transporter expression in the spontaneous hypertensive rat: Effect of stroke. J. Neurosci. Res. 2005, 79, 139-145.
45. Ullah, M. S.; Davies, A. J.; Halestrap, A. P. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1α-dependent mechanism. J. Biol. Chem. 2006, 281, 9030-9037.
46. Kay, H. H.; Zhu, S.; Tsoi, S. Hypoxia and lactate production in trophoblast cells. Placenta 2007, 28, 854-860.
47. Sonveaux, P.; Vegran, F.; Schroeder, T.; Wergin, M. C.; Verrax, J.; Rabbani, Z. N.; de Saedeleer, C. J.; Kennedy, K. M.; Diepart, C.; Jordan, B. F.; et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J. Clin. Investig. 2008, 118, 3930-3942.
48. De Heredia, P. F.; Wood, I. S.; Trayhurn, P. Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Pflugers Arch. 2010, 459, 509-518.
49. Wilson, M. C.; Meredith, D.; Fox, J. E.; Manoharan, C.; Davies, A. J.; Halestrap, A. P. Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4: The ancillary protein for the insensitive MCT2 is EMBIGIN (gp70). J. Biol. Chem. 2005, 280, 27213-27221.
50. Deora, A. A.; 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, 16245-16250.
51. Biswas, C.; Zhang, Y.; de Castro, R.; Guo, H.; Nakamura, T.; Kataoka, H.; Nabeshima, K. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995, 55, 434-439.
52. Wilson, M. C.; Meredith, D.; Halestrap, A. P. Fluorescence resonance energy transfer studies on the interaction between the lactate transporter MCT1 and CD147 provide information on the topology and stoichiometry of the complex in situ. J. Biol. Chem. 2002, 277, 3666-3672.
53. Pinheiro, C.; Longatto-Filho, A.; Scapulatempo, C.; Ferreira, L.; Martins, S.; Pellerin, L.; Rodrigues, M.; Alves, V. A. F.; Schmitt, F.; Baltazar, F. Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Arch. 2008, 452, 139-146.
54. Pinheiro, C.; Longatto-Filho, A.; Ferreira, L.; Pereira, S. M.; Etlinger, D.; Moreira, M. A.; Jubé, L. F.; Queiroz, G. S.; Schmitt, F.; Baltazar, F. Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma. Int. J. Gynecol. Pathol. 2008, 27, 568-574.
55. Miranda-Goncalves, V.; Honavar, M.; Pinheiro, C.; Martinho, O.; Pires, M. M.; Pinheiro, C.; Cordeiro, M.; Bebiano, G.; Costa, P.; Palmeirim, I.; et al. Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets. Neuro-Oncol. 2013, 15, 172-188.
56. Pinheiro, C.; Albergaria, A.; Paredes, J.; Sousa, B.; Dufloth, R.; Vieira, D.; Schmitt, F.; Baltazar, F. Monocarboxylate transporter 1 is up-regulated in basal-like breast carcinoma. Histopathology 2010, 56, 860-867.
57. Koukourakis, M. I.; Giatromanolaki, A.; Bougioukas, G.; Sivridis E. Lung cancer: A comparative study of metabolism related protein expression in cancer cells and tumor associated stroma. Cancer Biol. Ther. 2007, 6, 1476-1479.
58. Chen, H.; Wang, L.; Beretov, J.; Hao, J.; Xiao, W.; Li, Y. Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression. Clin. Exp. Metastasis 2010, 27, 557-569.
59. Porporato, P. E.; Dhup, S.; Dadhich, R. K.; Copetti, T.; Sonveaux, P. Anticancer targets in the glycolytic metabolism of tumors: a comprehensive review. Front. Pharmacol. 2011, 2, 49.
60. Colen, C. B.; Shen, Y.; Ghoddoussi, F.; Yu, P.; Francis, T. B.; Koch, B. J.; Monterey, M. D.; Galloway, M. P.; Sloan, A. E.; Mathupala, S. P. Metabolic targeting of lactate efflux by malignant glioma inhibits invasiveness and induces necrosis: An in vivo study. Neoplasia 2011, 13, 620-632.
61. Wahl, M. L.; Owen, J. A.; Burd, R.; Herlands, R. A.; Nogami, S. S.; Rodeck, U.; Berd, D.; Leeper, D. B.; Owen, C. S. Regulation of intracellular pH in human melanoma: Potential therapeutic implications. Mol. Cancer Ther. 2002, 1, 617-628.
62. Morais-Santos, F.; Miranda-Goncalves, V.; Pinheiro, S.; Vieira, A. F.; Paredes, J.; Schmitt, F. C.; Baltazar, F.; Pinheiro, C. Differential sensitivities to lactate transport inhibitors of breast cancer cell lines. Endocr.-Relat. Cancer 2014, 21, 27-38.
63. + symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors. Proc. Natl Acad. Sci. USA 2011, 108, 16663-16668.
64. Mathupala, S. P.; Parajuli, P.; Sloan, A. E. Silencing of monocarboxylate transporters via small interfering ribonucleic acid inhibits glycolysis and induces cell death in malignant glioma: An in vitro study. Neurosurgery 2004, 55, 1410-1419.
65. Gallagher, S. M.; Castorino, J. J.; Philp, N. J. Interaction of monocarboxylate transporter 4 with β1-integrin and its role in cell migration. Am. J. Physiol. Cell Physiol. 2009, 296, C414-C421.
66. Gallagher, S. M.; Castorino, J. J.; Wang, D.; Philp, N. J. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231. Cancer Res. 2007, 67, 4182-4189.
67. Kim, H. S.; Masko, E. M.; Poulton, S. L.; Kennedy, K. M.; Pizzo, S. V.; Dewhirst, M. W.; Freedland, S. J. Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer. BJU Int. 2012, 110, 1062-1069.
68. Hao, J.; Chen, H.; Madigan, M. C.; Cozzi, P. J.; Beretov, J.; Xiao, W.; Delprado, W. J.; Russell, P. J.; Li, Y. Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression. Br. J. Cancer 2010, 103, 1008-1018.
69. Pertega-Gomes, N.; Vizcaino, J. R.; Miranda-Goncalves, V.; Pinheiro, C.; Silva, J.; Pereira, H.; Monteiro, P.; Henrique, R. M.; Reis, R. M.; Lopes, C.; et al. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer 2011, 11, 312.
70. Pertega-Gomes, N.; Vizcaino, J. R.; Gouveia, C.; Jeronimo, C.; Henrique, R. M.; Lopes, C.; Baltazar, F. Monocarboxylate transporter 2 (MCT2) as putative biomarker in prostate cancer. Prostate 2013, 73, 763-769.
71. Martinez-Outschoorn, U. E.; Lisanti, M. P.; Sotgia, F. Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth. Semin. Cancer Biol. 2014, 25, 47-60.
72. Lisanti, M. P.; Martinez-Outschoorn, U. E.; Sotgia, F. Oncogenes induce the cancer-associated fibroblast phenotype: Metabolic symbiosis and "fibroblast addiction" are new therapeutic targets for drug discovery. Cell Cycle 2013, 12, 2723-2732.
73. Martinez-Outschoorn, U.; Sotgia, F.; Lisanti, M. P. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function. Semin. Oncol. 2014, 41, 195-216.
74. Martinez-Outschoorn, U. E.; Whitaker-Menezes, D.; Valsecchi, M.; Martinez-Cantarin, M. P.; Dulau-Florea, A.; Gong, J.; Howell, A.; Flomenberg, N.; Pestell, R. G.; Wagner, J.; et al. Reverse Warburg effect in a patient with aggressive B-cell lymphoma: Is lactic acidosis a paraneoplastic syndrome? Semin. Oncol. 2013, 40, 403-418.
75. Fiaschi, T.; Marini, A.; Giannoni, E.; Taddei, M. L.; Gandellini, P.; de Donatis, A.; Lanciotti, M.; Serni, S.; Cirri, P.; Chiarugi, P. Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay. Cancer Res. 2012, 72, 5130-5140.
76. Sanita, P.; Capulli, M.; Teti, A.; Galatioto, G. P.; Vicentini, C.; Chiarugi, P.; Bologna, M.; Angelucci, A. Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression. BMC Cancer 2014, 14, 154.
77. Pertega-Gomes, N.; Vizcaino, J. R.; Attig, J.; Jurmeister, S.; Lopes, C.; Baltazar, F. A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancer. BMC Cancer 2014, 14, 352.
78. Czernin, J.; Benz, M. R.; Allen-Auerbach, M. S. PET imaging of prostate cancer using C-acetate. PET Clin. 2009, 4, 163-172.
79. Flavin, R.; Zadra, G.; Loda, M. Metabolic alterations and targeted therapies in prostate cancer. J. Pathol. 2011, 223, 283-294.