Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44

Céline Pinheiro,Sara Ricardo,Fátima Baltazar,Adhemar Longatto-Filho,Rui M Reis,Fernando Schmitt

doi:10.1155/2010/427694

Abstract

Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.

Highlights

Uncontrolled tumour cell proliferation is a pivot mechanism in tumourigenesis, which leads to significant metabolic changes
The underlying molecular events involved in Monocarboxylate transporters (MCTs) regulation are poorly understood; it was recently demonstrated that proper plasma membrane expression and activity of MCTs, MCT1 and MCT4, require the presence of a chaperone, CD147 [7,8,9], known as EMMPRIN and basigin
Positive MCT1 expression was observed in both plasma membrane and cytoplasm (Figures 2(a) and 2(e)), while MCT2 expression was only observed in the cytoplasm (Figure 2(b)) and MCT4 was commonly found in the cytoplasm (Figure 2(c)) and rarely in the plasma membrane

Summary

Introduction

Uncontrolled tumour cell proliferation is a pivot mechanism in tumourigenesis, which leads to significant metabolic changes. Several plasma membrane transporters and exchangers have been implicated in the maintenance of the intracellular pH of cancer cells, by exporting the accumulating acid, leading to acidification of the extracellular milieu [3]. The MCT family comprises fourteen members, being the isoforms 1, 2, 3, and 4 responsible for the H+-linked transport of monocarboxylates such as lactic acid across the plasma membrane [6]. The underlying molecular events involved in MCT regulation are poorly understood; it was recently demonstrated that proper plasma membrane expression and activity of MCTs, MCT1 and MCT4, require the presence of a chaperone, CD147 [7,8,9], known as EMMPRIN and basigin.

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Conclusion