Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis.

Sandra Fernandes Martins,Rui Manuel Reis,Ricardo Filipe Alves Costa,Ricardo Amorim,Ana Preto,Adhemar Longatto-Filho,Carla Couto,Céline Pinheiro,Fernando Pardal,Mesquita Rodrigues,Sara Alves,Fátima Baltazar,Marta Viana-Pereira,Patrícia Silva,Joaquim Falcão,Herlander Marques,Sónia Vilaça,Sara Fernandes

doi:10.1186/s12885-016-2566-9

Abstract

BackgroundColorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis.MethodsExpressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry.ResultsAll proteins were overexpressed in primary CRC, lymph node and hepatic metastasis, when compared with non-neoplastic tissue, with exception of MCT1 in lymph node and hepatic metastasis. MCT1 and MCT4 expressions were associated with CD147 and GLUT1 in primary CRC. These markers were associated with clinical pathological features, reflecting the putative role of these metabolism-related proteins in the CRC setting.ConclusionThese findings provide additional evidence for the pivotal role of MCTs in CRC maintenance and progression, and support the use of MCTs as biomarkers and potential therapeutic targets in primary and metastatic CRC.

Highlights

Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide
MCT4, CD147 and GLUT1 are overexpressed in CRC primary tumours, lymph node and hepatic metastasis To infer about the importance of the proteins MCT1, MCT4, CD147 and GLUT1 in the progression of CRC, their expression was evaluated by immunohistochemistry in 487 samples of CRC, 210 samples of CRC lymph node metastasis and 45 samples of hepatic metastasis
All proteins were overexpressed at the plasma membrane of primary CRC tumours, CRC lymph node metastasis and CRC hepatic metastasis when compared with CRC normal adjacent (NA) tissue (p < 0.001, Fig. 2), with exception for MCT1 in CRC lymph node and hepatic metastasis

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is exported to the microenvironment by monocarboxylate transporters (MCTs). Most cancer cells display high rates of glycolysis with production of lactic acid, which is exported to the microenvironment, leading. Our group described higher MCT1 and MCT4 CRC membrane expression and lower of MCT2 expression, comparing with the adjacent normal tissue [32]. Despite these controversies, positive MCT4 expression in CRC has been associated with poor prognosis [33, 34], supporting the role of this MCT isoform in CRC malignancy. SMCT1 expression is frequently silenced in aberrant colon precursor lesions and cancer [40, 41]

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