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Significance of monocarboxylate transporter (MCT) expression in human tumors

2014; Frontiers Media; Volume: 5; Linguagem: Inglês

10.3389/conf.fphar.2014.61.00004

1663-9812

Baltazar Fatima,

Metabolism, Diabetes, and Cancer

Event Abstract Back to Event Significance of monocarboxylate transporter (MCT) expression in human tumors Fatima Baltazar1* 1 University of Minho, Portugal Background and aim. One essential hallmark of tumour cells is the Warburg effect in which cells upregulate glycolysis, even in the presence of oxygen. The high rates of glycolysis lead to increased production of lactate, which must be transported out of the cells. Monocarboxylate transporters (MCTs) play a key role in the maintenance of glycolysis, by performing the plasma membrane efflux of lactate coupled with a proton, especially the isoforms 1 (MCT1) and 4 (MCT4). Results. Our group has been studying the expression of these MCT isoforms as well as their chaperone, CD147, known to be essential for MCT activity and plasma membrane expression, in several series of human cancers. We found upregulation of MCT1 and MCT4 in the plasma membrane of colorectal cancer, upregulation of MCT1, MCT4 and CD147 in cervical cancer, upregulation of MCT1 in breast cancer and upregulation of MCT1 and CD147 in glioblastomas, when compared to the corresponding non-neoplastic tissues. On the other hand, there was downregulation of MCT4 in gastric cancer and downregulation of MCT1 in prostate cancer. We also found important associations between MCT overexpression and the clinicopathological data of the cases, mostly with aggressiveness parameters. We have been also targeting lactate transport in in vitro and in vivo models. In gliomas, inhibition of lactate transport (with CHC or MCT1 downregulation) decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT1/CD147 membrane expression. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. Conclusions / Discussion. Altogether, our results and the ones from other groups support lactate transporters as promising targets in cancer therapy. Acknowledgements FCT grant ref. PTDC/SAU-FCF/104347/2008, under the scope of “Programa Operacional Temático Factores de Competitividade” (COMPETE) of “Quadro Comunitário de Apoio III” and co-financed by Fundo Comunitário Europeu FEDER. References 1. 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, Feb;44(1):127-139. 2. Miranda-Gonçalves V, Honavar M, Pinheiro C, Martinho O, Cordeiro M, Bebiano G, Costa, Reis RM, Baltazar F. Monocarboxylate transporters (MCTs) in gliomas: Expression and exploitation as therapeutic targets, Neuro-Oncology, 2013, 15(2):172-188. Keywords: monocarboxylate transporters, solid tumours, therapeutic targets, CD147-Basigin, Warburg effect Conference: 4th Annual Meeting of the International Society of Proton Dynamics in Cancer, Garching, Germany, 10 Oct - 12 Oct, 2013. Presentation Type: Abstract Topic: 2. Membrane transporter in intracellular and extracellular pH-control Citation: Baltazar F (2014). Significance of monocarboxylate transporter (MCT) expression in human tumors. Front. Pharmacol. Conference Abstract: 4th Annual Meeting of the International Society of Proton Dynamics in Cancer. doi: 10.3389/conf.fphar.2014.61.00004 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Jan 2014; Published Online: 07 Feb 2014. * Correspondence: Prof. Fatima Baltazar, University of Minho, Braga, Portugal, fbaltazar@med.uminho.pt Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Fatima Baltazar Google Fatima Baltazar Google Scholar Fatima Baltazar PubMed Fatima Baltazar Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.