Abstract
BackgroundSoft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs).MethodsImmunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients’ clinical-pathological parameters.ResultsMCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival.ConclusionsThe present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients’ prognosis, while nuclear expression is associated with better prognosis.
Highlights
Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients
The expression of these proteins was mainly found at the plasma membrane (Figure 1), with the exception of MCT2 (Figure 1B), which was only observed in the plasma membrane in one case
MCT1 plasma membrane expression was depicted in 52 cases (60.5%, Figure 1A), MCT2 expression was found in 81 cases (94.2%), MCT4 was observed in the plasma membrane of 49 cases (57.0%, Figure 1C), while CD147 was found in 38 cases (44.2%, Figure 1D)
Summary
Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. We hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs). Since the hyper-glycolytic phenotype will generate high amounts of lactate inside cancer cells, monocarboxylate transporters (MCTs) play an important role in the extrusion of lactate, contributing to the maintenance of the intracellular pH of tumor cells. MCT2 is a high affinity transporter, being adapted to the uptake of monocarboxylates into cells, and is mostly found in tissues that use lactate as a respiratory fuel. MCT4 is known as a low affinity transporter and has been observed in highly glycolytic tissues, where is essentially responsible for lactate efflux. MCT1 and MCT4 are the best studied isoforms in cancer, as being responsible for lactate transport across the plasma membrane [9]
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