Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

Journal of Translational Medicine

Fátima Baltazar⁵  Rui M Reis²  Fernando C Schmitt¹  Daniela Ribeiro⁶  Isabel Valença⁶  Sandra Morini⁴  Marcus V Olivieri³  Emílio C Curcelli⁷  Guilherme Ribeiro²  Lucas F Abrahão-Machado⁴  Filipa Morais-Santos⁵  Valter Penna³  Céline Pinheiro² 

[1] Medical Faculty, University of Porto, Porto, Portugal;Molecular Oncology Research Center, Barretos Cancer Hospital, Pio XII Foundation, São Paulo, Barretos, Brazil;Department of Orthopedics, Barretos Cancer Hospital, Pio XII Foundation, São Paulo, Barretos, Brazil;Department of Pathology, Barretos Cancer Hospital, Pio XII Foundation, São Paulo, Barretos, Brazil;ICVS/3B’s - PT Government Associate Laboratory, Guimarães, Braga, Portugal;Centre for Cell Biology and Department of Biology, University of Aveiro, Aveiro, Portugal;Medical Faculty, UNESP, Botucatu, São Paulo, Brazil

关键词: Prognosis;    Soft tissue sarcoma;    CD147/EMMPRIN;    Monocarboxylate transporters;   

Others  :  814093
DOI  :  10.1186/1479-5876-12-118

 received in 2013-10-04, accepted in 2014-04-28,  发布年份 2014

【 摘 要 】

Background

Soft 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).

Methods

Immunohistochemical 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.

Results

MCT1, 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.

Conclusions

The 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.

【 授权许可】

   
2014 Pinheiro et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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