Abstract
BackgroundMonocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma.MethodsProstate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs) blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171), adjacent non-neoplastic tissues (n = 135), PIN lesions (n = 40) and normal prostatic tissue (n = 14). Protein expression was correlated with patients' clinicopathologic characteristics.ResultsIn the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence.ConclusionsOur data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and both MCT4 and CD147 as markers of poor prognosis in prostate cancer.
Highlights
Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, the role of monocarboxylate transporters (MCTs) in prostate cancer is largely unknown
The aim of the present study was to assess the role of MCTs in prostate cancer, by comparing the immunohistochemical expression of the MCT isoforms 1, 2 and 4, along with CD147 and gp70, in normal prostatic tissue, adjacent non-neoplastic tissue, PIN lesions and neoplastic tissues in a large series of prostate samples organized into tissue microarrays (TMAs), and evaluating their clinico-pathological value
MCT, CD147 and gp70 expressions in prostate tissues A total of 346 prostate samples organised into TMAs, including 135 non-neoplastic, 40 PIN lesions and 171 neoplastic tissues were analysed for MCT1, MCT isoform 2 (MCT2), MCT4, CD147 and gp70 expressions
Summary
Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, the role of MCTs in prostate cancer is largely unknown. MCTs are proteins that facilitate the transmembrane transport of short-chain fatty acids, such as pyruvate and lactate, coupled with a proton. In glycolytic tumours, they promote the efflux of lactic acid, constituting important players in the maintenance of tumour intracellular pH, as well as in the maintenance of the high rates of glycolysis [4,5]. MCTs play a central role in tumour metabolism and, as a result, constitute attractive targets in cancer therapy which have not been explored yet
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