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iConcept Journal of Emerging Issues in Medical Diagnosis and Treatment
Title
iConcept Journal of Emerging Issues in Medical Diagnosis and Treatment
Editor
Eugenia Giannopoulou
ISSN
2309-3528
Publisher
iConcept Press

iConcept Journal of Emerging Issues in Medical Diagnosis and Treatment

Diagnostic and Prognostic Value of Lactate Transporters in Prostate Cancer

by Nelma Pértega-Gomes, José Ramón Vizcaíno, Carlos Lopes and Fatima Baltazar

Volume: 2 (2013); Issue: 6

Abstract

Prostate cancer is one of the most common cancers diagnosed in men. Most prostate cancer–related deaths are due to advanced disease, which results from any combination of lymphatic, blood, or contiguous local spread and further proliferation. Thus, cancer cells must generate enough energy and acquire or synthesize biomolecules at a sufficient rate to meet the demands of proliferation. By extension, it is not surprising that tumor cells often display fundamental changes in pathways of energy metabolism and nutrient uptake to meet the increased requirements of proliferation. Nonetheless, the metabolic phenotype of cancer cells is often neglected in cancer research, which typically focuses on mutational mechanisms of cancer progression. Otto Warburg was the first to report that cancer cells, and many cells grown in-vitro, exhibit glucose fermentation even when enough oxygen is present. It is now widely accepted by many researchers that increased glucose consumption is a hallmark of malignant cells. The consequent high glycolytic rates induce an acidic tumour environment, which is associated with enhancement of several malignant features. While these observations are widespread, their molecular underpinnings have yet to be discovered. Monocarboxylate transporters (MCTs) are proteins that facilitate the transmembrane transport of short-chain fatty acids, such as pyruvate and lactate. In glycolytic tumours, MCT1 and MCT4 mediate the efflux of lactic acid coupled with a proton, constituting important players in the maintenance of tumor intracellular pH, as well as in the maintenance of the high rates of glycolysis. Therefore, these lactate transporters play a central role in tumour metabolism and, as a result, constitute attractive targets in cancer therapy, which are now starting to be explored in the clinical context. Upregulation of MCTs has been shown in several solid tumours, such as colorectal carcinomas, uterine cervix carcinomas and breast carcinomas. Regarding prostate cancer, at variance with other solid tumors, there is no up-regulation of MCT1, MCT4 or CD147 (MCT1/MCT4 chaperone) at the plasma membrane of prostate cancer cells. However, a significant increase in both MCT2 and MCT4 cytoplasmic expressions, accompanied by a decrease in MCT1 and CD147 plasma membrane expressions from normal to tumour tissue. CD147 expression correlated with both MCT1 and MCT4 but not with MCT2. Importantly, MCT4 and CD147 were associated with markers of poor prognosis. These findings point to the involvement of MCT4 and its chaperone in the malignant phenotype of prostate cancer. Also, it appears that prostate cancer is not as glycolytic as other tumour types. These observations could have important consequences in prognostic and therapeutic strategies involving metabolic targets in prostate cancer.

Author Details

Nelma Pértega-Gomes
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Portugal, Portugal
José Ramón Vizcaíno
Department of Pathology, Centro Hospitalar do Porto, Portugal, Portugal
Carlos Lopes
Department of Pathology, Centro Hospitalar do Porto, Portugal, Portugal
Fatima Baltazar
Life and Health Sciences Research Institute, University of Minho, Portugal, Portugal

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