Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report)
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urnal of Translational Medicine Open Access
RESEARCH
Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report) Irene Dell’Anno1†, Elisa Barone1†, Luciano Mutti2†, Doris M. Rassl3, Stefan J. Marciniak4, Roberto Silvestri1, Stefano Landi1* and Federica Gemignani1
Abstract Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the pleura, mainly related to asbestos exposure. As in other solid tumors, malignant cells exhibit high glucose uptake and glycolytic rates with increased lactic acid efflux into the interstitial space. Lactate transport into and out of cells, crucial to maintaining intracellular pH homeostasis and glycolysis, is carried out by monocarboxylate transporters (MCTs) and the chaperone basigin (CD147). We set out to examine the clinical significance of basigin, MCT1 and MCT4 in the context of MPM and to evaluate their expression in relation to the evolution of the disease. Methods: We used immunohistochemistry to measure the expression of basigin, MCT1 and MCT4 in a cohort of 135 individuals with MPM compared to a series of 15 non-MPM pleura specimens. Moreover, by Kaplan–Meier and Cox analyses we evaluated whether an expression over the average of these markers could be associated with the patients’ overall survival (OS). Results: We detected positive staining of basigin, MCT1, and MCT4 in most MPM specimens. In particular, MCT4 was always positive in malignant tissues but undetectable in the 4 normal pleural specimens incorporated within the tissue microarray. This was confirmed in the additional series of 15 normal pleural samples. Moreover, MCT4 expression was significantly associated with reduced OS. Conclusion: In this study, the tissue expression of basigin did not prove to be exploitable as a diagnostic or prognostic marker for MPM patients. The expression of MCT1 was not informative either, being tightly correlated with that of basigin. However, the expression of MCT4 showed promise as a diagnostic/therapeutic and prognostic biomarker. Keywords: Malignant pleural mesothelioma (MPM), MCT1, MCT4, Basigin (CD147), Immunohistochemistry (IHC), Tissue microarray (TMA) Background It is well-known that cancer cells can obtain energy by increasing their rates of glycolysis despite oxygen being available (Warburg effect) [1]. This metabolic shift *Correspondence: [email protected] † Irene Dell’Anno, Elisa Barone and Luciano Mutti contributed equally to this work 1 Department of Biology, University of Pisa, Pisa, Toscana, Italy Full list of author information is available at the end of the article
generates intracellular lactic acid that is actively expelled causing extracellular acidification. Low interstitial pH has been associated with increased levels of VEGF, IL8, and heparanase that could trigger cancer autocrine stimulation and enhance tumor aggressiveness [2]. Indeed, the accumulation of lactate in a wider range of solid cancers has been correlated with poor clinical outcome [3]. The monocarboxyla
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