{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:56:30Z","timestamp":1775267790872,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2011,7,25]],"date-time":"2011-07-25T00:00:00Z","timestamp":1311552000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1\/4 and MCT2 chaperones, respectively, in prostate carcinoma.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs) blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171), adjacent non-neoplastic tissues (n = 135), PIN lesions (n = 40) and normal prostatic tissue (n = 14). Protein expression was correlated with patients' clinicopathologic characteristics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and both MCT4 and CD147 as markers of poor prognosis in prostate cancer.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-11-312","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T06:21:37Z","timestamp":1311661297000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":144,"title":["Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer"],"prefix":"10.1186","volume":"11","author":[{"given":"Nelma","family":"P\u00e9rtega-Gomes","sequence":"first","affiliation":[]},{"given":"Jos\u00e9 R","family":"Vizca\u00edno","sequence":"additional","affiliation":[]},{"given":"Vera","family":"Miranda-Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"C\u00e9line","family":"Pinheiro","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Silva","sequence":"additional","affiliation":[]},{"given":"Helena","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Monteiro","sequence":"additional","affiliation":[]},{"given":"Rui M","family":"Henrique","sequence":"additional","affiliation":[]},{"given":"Rui M","family":"Reis","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Lopes","sequence":"additional","affiliation":[]},{"given":"F\u00e1tima","family":"Baltazar","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2011,7,25]]},"reference":[{"key":"2799_CR1","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1085\/jgp.8.6.519","volume":"8","author":"O Warburg","year":"1927","unstructured":"Warburg O, Wind F, Neglein E: Metabolism of tumours in the body. J Gen Physiol. 1927, 8: 519-530. 10.1085\/jgp.8.6.519.","journal-title":"J Gen Physiol"},{"key":"2799_CR2","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1038\/nrc1478","volume":"4","author":"RA Gatenby","year":"2004","unstructured":"Gatenby RA, Gillies RJ: Why do cancers have high aerobic glycolysis?. Nat Rev Cancer. 2004, 4: 891-899. 10.1038\/nrc1478.","journal-title":"Nat Rev Cancer"},{"key":"2799_CR3","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/S0305-7372(03)00106-3","volume":"29","author":"H Izumi","year":"2003","unstructured":"Izumi H, Torigoe T, Ishiguchi H, Uramoto H, Yoshida Y, Tanabe M, Ise T, Murakami T, Yoshida T, Nomoto M, Kohno K: Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer Treat Rev. 2003, 29: 541-549. 10.1016\/S0305-7372(03)00106-3.","journal-title":"Cancer Treat Rev"},{"key":"2799_CR4","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1002\/0470868716.ch17","volume":"240","author":"GL Semenza","year":"2001","unstructured":"Semenza GL, Artemov D, Bedi A, Bhujwalla Z, Chiles K, Feldser D, Laughner E, Ravi R, Simons J, Taghavi P, Zhong H: The metabolism of tumours: 70 years later. Novartis Found Symp. 2001, 240: 251-260.","journal-title":"Novartis Found Symp"},{"key":"2799_CR5","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1042\/bj3430281","volume":"343","author":"AP Halestrap","year":"1999","unstructured":"Halestrap AP, Price NT: The proton-linked monocarboxylate transporter MCT. Family: structure, function and regulation. Biochem J. 1999, 343: 281-299. 10.1042\/0264-6021:3430281.","journal-title":"Biochem J"},{"key":"2799_CR6","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s00428-007-0558-5","volume":"452","author":"C Pinheiro","year":"2008","unstructured":"Pinheiro C, Longatto-Filho A, Scapulatempo C, Ferreira L, Martins S, Pellerin L, Rodrigues M, Alves VA, Schmitt F, Baltazar F: Increased expression of monocarboxylate transporters 1, 2 and 4 in colorectal carcinomas. Virchows Arch. 2008, 452: 139-146. 10.1007\/s00428-007-0558-5.","journal-title":"Virchows Arch"},{"key":"2799_CR7","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1097\/PGP.0b013e31817b5b40","volume":"27","author":"C Pinheiro","year":"2008","unstructured":"Pinheiro C, Longatto-Filho A, Ferreira L, Pereira S, Etlinger D, Moreira M, Jub\u00e9 L, Queiroz G, Schmitt F, Baltazar F: Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma. Int J Gynec Pathol. 2008, 27: 568-574. 10.1097\/PGP.0b013e31817b5b40.","journal-title":"Int J Gynec Pathol"},{"key":"2799_CR8","first-page":"617","volume":"37","author":"ML Wahl","year":"2002","unstructured":"Wahl ML, Owen JA, Burd R, Herlands RA, Nogami S, Rodeck U, Berd D, Leeper DB, Owen CS: Regulation of intracellular pH in human melanoma:potential therapeutic implications. Mol Cancer Ther. 2002, 37: 617-628.","journal-title":"Mol Cancer Ther"},{"key":"2799_CR9","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1111\/j.1365-2559.2010.03560.x","volume":"56","author":"C Pinheiro","year":"2010","unstructured":"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. 10.1111\/j.1365-2559.2010.03560.x.","journal-title":"Histopathology"},{"key":"2799_CR10","doi-asserted-by":"publisher","first-page":"427694","DOI":"10.1155\/2010\/427694","volume":"2010","author":"C Pinheiro","year":"2010","unstructured":"Pinheiro C, Reis RM, Ricardo S, Longatto-Filho A, Schmitt F, Baltazar F: Expression of monocarboxylate transporters 1, 2, and 4 in human tumours and their association with CD147 and CD44. J Biomed Biotechnol. 2010, 2010: 427694-Epub 2010 May 4","journal-title":"J Biomed Biotechnol"},{"key":"2799_CR11","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.4161\/cbt.6.9.4635","volume":"6","author":"MI Koukourakis","year":"2007","unstructured":"Koukourakis MI, Giatromanolaki A, Bougioukas G, Sivridis E: Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumour associated stroma. Cancer Biol Ther. 2007, 6: 1476-1479. 10.4161\/cbt.6.9.4635.","journal-title":"Cancer Biol Ther"},{"issue":"Supplement: Sup","key":"2799_CR12","first-page":"233","volume":"455","author":"N Gomes","year":"2009","unstructured":"Gomes N, Vizca\u00edno JR, Pinheiro C, Baltazar F: Monocarboxylate transporters 2 and 4 are upregulated in prostate carcinoma. Virchows Arch. 2009, 455 (Supplement: Suppl. 1): 233-","journal-title":"Virchows Arch"},{"issue":"Supplement S3","key":"2799_CR13","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1017\/S1431927609990547","volume":"15","author":"N Gomes","year":"2009","unstructured":"Gomes N, Vizca\u00edno JR, Pinheiro C, Baltazar F: Characterization of monocarboxylate transporters expression in prostate carcinoma. Microsc Microanal. 2009, 15 (Supplement S3): 17-18.","journal-title":"Microsc Microanal"},{"issue":"7","key":"2799_CR14","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1038\/sj.bjc.6605839","volume":"103","author":"J Hao","year":"2010","unstructured":"Hao J, Chen H, Madigan MC, Cozzi PJ, Beretov J, Xiao W, Delprado WJ, Russell PJ, Li Y: Co-expression of CD147 (EMMPRIN), CD44v3-10, MDRI and monocarboxylate transporters is associated with prostate cancer drug resistance and progression. Br J Cancer. 2010, 103 (7): 1008-1018. 10.1038\/sj.bjc.6605839.","journal-title":"Br J Cancer"},{"key":"2799_CR15","doi-asserted-by":"publisher","first-page":"3896","DOI":"10.1093\/emboj\/19.15.3896","volume":"19","author":"P Kirk","year":"2000","unstructured":"Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP: CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J. 2000, 19: 3896-3904. 10.1093\/emboj\/19.15.3896.","journal-title":"EMBO J"},{"key":"2799_CR16","doi-asserted-by":"publisher","first-page":"27213","DOI":"10.1074\/jbc.M411950200","volume":"280","author":"MC Wilson","year":"2005","unstructured":"Wilson MC, Meredith D, Fox JE, Manoharan C, Davies AJ, Halestrap AP: 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. 10.1074\/jbc.M411950200.","journal-title":"J Biol Chem"},{"key":"2799_CR17","doi-asserted-by":"publisher","first-page":"16245","DOI":"10.1073\/pnas.0504419102","volume":"102","author":"AA Deora","year":"2005","unstructured":"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: 16245-16250. 10.1073\/pnas.0504419102.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2799_CR18","doi-asserted-by":"publisher","first-page":"4182","DOI":"10.1158\/0008-5472.CAN-06-3184","volume":"67","author":"SM Gallagher","year":"2007","unstructured":"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 MDA-MB-231. Cancer Res. 2007, 67: 4182-4189. 10.1158\/0008-5472.CAN-06-3184.","journal-title":"Cancer Res"},{"key":"2799_CR19","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1111\/j.1440-1827.2006.01972.x","volume":"56","author":"K Nabeshima","year":"2006","unstructured":"Nabeshima K, Iwasaki H, Koga K, Hojo H, Suzumiya J, Kikuchi M: Emmprin (basigin\/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression. Pathol Int. 2006, 56: 359-367. 10.1111\/j.1440-1827.2006.01972.x.","journal-title":"Pathol Int"},{"key":"2799_CR20","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.biochi.2004.09.023","volume":"87","author":"EE Gabison","year":"2005","unstructured":"Gabison EE, Hoang-Xuan T, Mauviel A, Menashi S: EMMPRIN\/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie. 2005, 87: 361-368. 10.1016\/j.biochi.2004.09.023.","journal-title":"Biochimie"},{"key":"2799_CR21","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1002\/ijc.22062","volume":"19","author":"S Riethdorf","year":"2006","unstructured":"Riethdorf S, Reimers N, Assmann V, Kornfeld JW, Terracciano L, Sauter G, Pantel K: High incidence of EMMPRIN expression in human tumors. Int J Cancer. 2006, 19: 1800-1810.","journal-title":"Int J Cancer"},{"key":"2799_CR22","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s12253-008-9131-z","volume":"15","author":"H Zhao-Dong","year":"2009","unstructured":"Zhao-Dong H, Xue-Cheng B, Wei-jun Q, He H, Dai Q, Zou J, Ye Y, Liang Y, Zeng G, Chen Z, Zhong W: CD147 Expression indicates unfavourable prognosis in prostate cancer. Pathol Oncol. 2009, 15: 369-374. 10.1007\/s12253-008-9131-z.","journal-title":"Pathol Oncol"},{"key":"2799_CR23","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1159\/000163852","volume":"75","author":"WD Zhong","year":"2008","unstructured":"Zhong WD, Han ZD, He HC, Bi XC, Dai QS, Zhu G, Ye YK, Liang YX, Qin WJ, Zhang Z, Zeng GH, Chen ZN: CD147, MMP-1, MMP-2 and MMP-9 protein expression as significant prognostic factors in human prostate cancer. Oncology. 2008, 75: 230-236. 10.1159\/000163852.","journal-title":"Oncology"},{"key":"2799_CR24","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1007\/s00262-008-0473-x","volume":"57","author":"MC Madigan","year":"2008","unstructured":"Madigan MC, Kingsley EA, Cozzi PJ, Madigan MC, Kingsley EA, Cozzi PJ, Delprado W, Russel P, Li Y: The role of extracellular matrix metalloproteinase inducer protein in prostate cancer progression. Cancer Immunol Immunother. 2008, 57: 1367-1379. 10.1007\/s00262-008-0473-x.","journal-title":"Cancer Immunol Immunother"},{"key":"2799_CR25","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.jss.2008.11.838","volume":"160","author":"ZD Han","year":"2010","unstructured":"Han ZD, He HC, Bi XC, Qin WJ, Dai QS, Zou J, Ye YK, Liang YX, Zeng GH, Zhu G, Chen ZN, Zhong WD: Expression and clinical significance of CD147 in genitourinary carcinomas. J Surg Res. 2010, 160: 260-267. 10.1016\/j.jss.2008.11.838.","journal-title":"J Surg Res"},{"key":"2799_CR26","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1097\/01.pas.0000173646.99337.b1","volume":"29","author":"J Epstein","year":"2005","unstructured":"Epstein J, Allsbrook W, Amin M, Egevad LL, ISUP Grading Committee: The 2005 International Society of Urological Pathology (ISUP) Consensus conference on gleason grading of prostatic carcinoma. Am J Sur Pathol. 2005, 29: 1228-1242. 10.1097\/01.pas.0000173646.99337.b1.","journal-title":"Am J Sur Pathol"},{"key":"2799_CR27","volume-title":"AJCC cancer staging manual","author":"SB Edge","year":"2010","unstructured":"Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A: AJCC cancer staging manual. 2010, Chicago:Springer, 7","edition":"7"},{"key":"2799_CR28","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1016\/S0140-6736(08)60729-1","volume":"371","author":"JE Damber","year":"2008","unstructured":"Damber JE, Aus G: Prostate cancer. Lancet. 2008, 371: 1710-1721. 10.1016\/S0140-6736(08)60729-1.","journal-title":"Lancet"},{"key":"2799_CR29","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1227\/01.NEU.0000143034.62913.59","volume":"55","author":"SP Mathupala","year":"2004","unstructured":"Mathupala SP, Parajuli P, Sloan AE: 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.","journal-title":"Neurosurgery"},{"key":"2799_CR30","first-page":"3930","volume":"118","author":"P Sonveaux","year":"2008","unstructured":"Sonveaux P, Vegran F, Schroeder T, Wergin M, Verrax J, Rabbani ZN, 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: 3930-3942.","journal-title":"J Clin Invest"},{"key":"2799_CR31","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1158\/0008-5472.CAN-08-2491","volume":"69","author":"MG Slomiany","year":"2009","unstructured":"Slomiany MG, Grass GD, Robertson AD: Hyaluronan, CD44, and emmprin regulate lactate efflux and membrane localization of monocarboxylate transporters in human breast carcinoma cells. Cancer Res. 2009, 69: 1293-1301. 10.1158\/0008-5472.CAN-08-2491.","journal-title":"Cancer Res"},{"key":"2799_CR32","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/0026-0495(87)90132-6","volume":"36","author":"A Legaspi","year":"1987","unstructured":"Legaspi A, Jeevanandam M, Starnes HF, Brennan MF: Whole body lipid and energy metabolism in the cancer patient. Metabolism. 1987, 36: 958-963. 10.1016\/0026-0495(87)90132-6.","journal-title":"Metabolism"},{"key":"2799_CR33","first-page":"2220","volume":"62","author":"J Luo","year":"2002","unstructured":"Luo J, Zha S, Gage WR, Dunn TA, Hicks JL, Bennett CJ, Ewing CM, Platz EA, Ferdinandusse S, Wanders RJ, Trent JM, Isaacs WB, De Marzo AM: \u03b1-Methylacyl-CoA racemase: a new molecular marker for prostate cancer. Cancer Res. 2002, 62: 2220-2226.","journal-title":"Cancer Res"},{"key":"2799_CR34","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/S0006-291X(03)00550-3","volume":"304","author":"G McClelland","year":"2003","unstructured":"McClelland G, Khanna S, Brooks G: Peroxisomal membrane monocarboxylate transporters: evidence for a redox shuttle system?. Biochem Biophys Res Commun. 2003, 304: 130-135. 10.1016\/S0006-291X(03)00550-3.","journal-title":"Biochem Biophys Res Commun"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-11-312.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2407-11-312\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-11-312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-11-312.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T21:07:11Z","timestamp":1630616831000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/1471-2407-11-312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7,25]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["2799"],"URL":"https:\/\/doi.org\/10.1186\/1471-2407-11-312","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7,25]]},"assertion":[{"value":"12 February 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"312"}}