Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression

详细信息    查看全文

• 作者：Patrizia Sanità (7)
  Mattia Capulli (7)
  Anna Teti (7)
  Giuseppe Paradiso Galatioto (8)
  Carlo Vicentini (8)
  Paola Chiarugi (9)
  Mauro Bologna (8)
  Adriano Angelucci (7)
  
• 关键词：Aerobic glycolysis ; Monocarboxylate transporters ; Cancer associated fibroblasts ; Warburg effect ; Tumor stroma
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,577 KB
• 参考文献：1. Warburg O: On the origin of cancer cells. / Science 1956, 123:309-14. CrossRef
  2. Moreno-Sanchez R, Rodriguez-Enriquez S, Marin-Hernandez A, Saavedra E: Energy metabolism in tumor cells. / FEBS J 2007, 274:1393-418. CrossRef
  3. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB: The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. / Cell Metab 2008, 7:11-0. CrossRef
  4. Roberts MJ, Schirra HJ, Lavin MF, Gardiner RA: Metabolomics: a novel approach to early and noninvasive prostate cancer detection. / Korean J Urol 2011, 52:79-9. CrossRef
  5. Garcia CK, Li X, Luna J, Francke U: cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2–p12. / Genomics 1994, 23:500-03. CrossRef
  6. Bonen A: The expression of lactate transporters (MCT1 and MCT4) in heart and muscle. / Eur J Appl Physiol 2001, 86:6-1. CrossRef
  7. Halestrap AP, Price NT: The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. / Biochem J 1999,343(Pt 2):281-99. CrossRef
  8. Cuff MA, Lambert DW, Shirazi-Beechey SP: Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1. / J Physiol 2002, 539:361-71. CrossRef
  9. Bergersen LH: Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes in brain and muscle. / Neuroscience 2007, 145:11-9. CrossRef
  10. Kuchiiwa T, Nio-Kobayashi J, Takahashi-Iwanaga H, Yajima T, Iwanaga T: Cellular expression of monocarboxylate transporters in the female reproductive organ of mice: implications for the genital lactate shuttle. / Histochem Cell Biol 2011, 135:351-60. CrossRef
  11. Hirschhaeuser F, Sattler UG, Mueller-Klieser W: Lactate: a metabolic key player in cancer. / Cancer Res 2011, 71:6921-925. CrossRef
  12. Pinheiro C, Longatto-Filho A, Azevedo-Silva J, Casal M, Schmitt FC, Baltazar F: Role of monocarboxylate transporters in human cancers: state of the art. / J Bioenerg Biomembr 2012, 44:127-39. CrossRef
  13. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP: The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. / Cell Cycle 2009, 8:3984-001. CrossRef
  14. Sonveaux P, Vegran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, Kelley MJ, Gallez B, Wahl ML, Feron O, Dewhirst MW: Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. / J Clin Invest 2008, 118:3930-942.
  15. Costello LC, Franklin RB, Narayan P: Citrate in the diagnosis of prostate cancer. / Prostate 1999, 38:237-45. CrossRef
  16. Swanson MG, Zektzer AS, Tabatabai ZL, Simko J, Jarso S, Keshari KR, Schmitt L, Carroll PR, Shinohara K, Vigneron DB, Kurhanewicz J: Quantitative analysis of prostate metabolites using 1H HR-MAS spectroscopy. / Magn Reson Med 2006, 55:1257-264. CrossRef
  17. Movsas B, Chapman JD, Horwitz EM, Pinover WH, Greenberg RE, Hanlon AL, Iyer R, Hanks GE: Hypoxic regions exist in human prostate carcinoma. / Urology 1999, 53:11-8. CrossRef
  18. Remmele W, Hildebrand U, Hienz HA, Klein PJ, Vierbuchen M, Behnken LJ, Heicke B, Scheidt E: Comparative histological, histochemical, immunohistochemical and biochemical studies on oestrogen receptors, lectin receptors, and Barr bodies in human breast cancer. / Virchows Arch A Pathol Anat Histopathol 1986, 409:127-47. CrossRef
  19. Sieh S, Taubenberger AV, Rizzi SC, Sadowski M, Lehman ML, Rockstroh A, An J, Clements JA, Nelson CC, Hutmacher DW: Phenotypic characterization of prostate cancer LNCaP cells cultured within a bioengineered microenvironment. / PLoS One 2012, 7:e40217. CrossRef
  20. Takebe K, Nio-Kobayashi J, Takahashi-Iwanaga H, Yajima T, Iwanaga T: Cellular expression of a monocarboxylate transporter (MCT1) in the mammary gland and sebaceous gland of mice. / Histochem Cell Biol 2009, 131:401-09. CrossRef
  21. Takebe K, Takahashi-Iwanaga H, Iwanaga T: Intensified expressions of a monocarboxylate transporter in consistently renewing tissues of the mouse. / Biomed Res 2011, 32:293-01. CrossRef
  22. Pertega-Gomes N, Vizcaino JR, Miranda-Goncalves V, Pinheiro C, Silva J, Pereira H, Monteiro P, Henrique RM, Reis RM, Lopes C, Baltazar F: Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. / BMC Cancer 2011, 11:312. CrossRef
  23. Hao J, Chen H, Madigan MC, Cozzi PJ, Beretov J, Xiao W, Delprado WJ, Russell PJ, Li Y: Co-expression of CD147 (EMMPRIN), CD44v3-0, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression. / Br J Cancer 2010, 103:1008-018. CrossRef
  24. Pellerin L, Magistretti PJ: Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. / Proc Natl Acad Sci U S A 1994, 91:10625-0629. CrossRef
  25. Johnson MT, Freeman EA, Gardner DK, Hunt PA: Oxidative metabolism of pyruvate is required for meiotic maturation of murine oocytes in vivo. / Biol Reprod 2007, 77:2-. CrossRef
  26. Py G, Eydoux N, Lambert K, Chapot R, Koulmann N, Sanchez H, Bahi L, Peinnequin A, Mercier J, Bigard AX: Role of hypoxia-induced anorexia and right ventricular hypertrophy on lactate transport and MCT expression in rat muscle. / Metabolism 2005, 54:634-44. CrossRef
  27. Ord JJ, Streeter EH, Roberts IS, Cranston D, Harris AL: Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer. / Br J Cancer 2005, 93:346-54. CrossRef
  28. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, Whitaker-Menezes D, Daumer KM, Lin Z, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Knudsen ES, Sotgia F, Lisanti MP: 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, 9:3256-276.
  29. Fiaschi T, Marini A, Giannoni E, Taddei ML, 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, 72:5130-140. CrossRef
  30. Martinez-Outschoorn UE, Lin Z, Trimmer C, Flomenberg N, Wang C, Pavlides S, Pestell RG, Howell A, Sotgia F, Lisanti MP: Cancer cells metabolically “fertilize-the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors. / Cell Cycle 2011, 10:2504-520. CrossRef
  31. Kim HS, Masko EM, Poulton SL, Kennedy KM, Pizzo SV, Dewhirst MW, Freedland SJ: Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer. / BJU Int 2012, 110:1062-069. CrossRef
  32. Maehama T, Patzelt A, Lengert M, Hutter KJ, Kanazawa K, Hausen H, Rosl F: Selective down-regulation of human papillomavirus transcription by 2-deoxyglucose. / Int J Cancer 1998, 76:639-46. CrossRef
  33. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/154/prepub
  
• 作者单位：Patrizia Sanità (7)
  Mattia Capulli (7)
  Anna Teti (7)
  Giuseppe Paradiso Galatioto (8)
  Carlo Vicentini (8)
  Paola Chiarugi (9)
  Mauro Bologna (8)
  Adriano Angelucci (7)
  
  7. Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, Coppito 2, 67100, L’Aquila, Italy
  8. Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100, L’Aquila, Italy
  9. Department of Biochemical Sciences, Tuscany Tumor Institute and “Center for Research, Transfer and High Education DenoTHE- University of Florence, 50134, Florence, Italy
  
• ISSN：1471-2407

文摘

Background Cancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism. Methods Role of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts. Moreover prostate tissues from carcinoma and benign hypertrophy cases were analyzed for individuating clinical-pathological implications of MCT1 and MCT4 expression. Results Transformed prostate epithelial (TPE) and prostate cancer (PCa) cells express both MCT1 and MCT4 and demonstrated variable dependence on aerobic glycolysis for maintaining their proliferative rate. In glucose-restriction the presence of L-lactate determined, after 24?h of treatment, in PCa cells the up-regulation of MCT1 and of cytochrome c oxidase subunit I (COX1), and reduced the activation of AMP-activated protein kinase respect to untreated cells. The blockade of MCT1 function, performed by si RNA silencing, determined an appreciable antiproliferative effect when L-lactate was utilized as energetic fuel. Accordingly L-lactate released by high glycolytic human diploid fibroblasts WI-38 sustained survival and growth of TPE and PCa cells in low glucose culture medium. In parallel, the treatment with conditioned medium from PCa cells was sufficient to induce glycolytic metabolism in WI-38 cells, with upregulation of HIF-1a and MCT4. Co-injection of PCa cells with high glycolytic WI-38 fibroblasts determined an impressive increase in tumor growth rate in a xenograft model that was abrogated by MCT1 silencing in PCa cells. The possible interplay based on L-lactate shuttle between tumor and stroma was confirmed also in human PCa tissue where we observed a positive correlation between stromal MCT4 and tumor MCT1 expression. Conclusions Our data demonstrated that PCa progression may benefit of MCT1 expression in tumor cells and of MCT4 in tumor-associated stromal cells. Therefore, MCTs may result promising therapeutic targets in different phases of neoplastic transformation according to a strategy aimed to contrast the energy metabolic adaptation of PCa cells to stressful environments.