Significance of monocarboxylate transporter (MCT) expression in human tumors

Abstract

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.