Caracterização da expressão dos transportadores de monocarboxilatos (MCTs) em sarcomas dos tecidos moles: Impacto prognóstico distinto da localização subcelular de MCT1

Os sarcomas de tecidos moles (STS) são um grupo de tumores, que, apesar dos avanços terapêuticos atuais, ainda estão associados a um mau prognóstico em metade dos pacientes. No presente estudo, a expressão e significado clinico-patológico dos transportadores de monocarboxilatos (MCTs), importantes proteínas envolvidas na reprogramação metabólica das células tumorais, foram avaliados numa série de 86 STS. De salientar que foi observada associação entre a expressão dos MCTs e variáveis de pior prognóstico.  Ainda, é mostrada pela primeira vez expressão nuclear de MCT1, a qual está associada a variáveis de melhor prognóstico.

Autores e afiliações:

Céline Pinheiro^1,2,3,4; Valter Penna⁵; Filipa Morais-Santos^1,2; Lucas F. Abrahão-Machado⁶; Guilherme Ribeiro⁴; Emílio C. Curcelli⁷; Marcus V. Olivieri⁵; Sandra Morini⁶; Isabel Valença⁸; Daniela Ribeiro⁸; Fernando C. Schmitt^9,10,11_; Rui M. Reis^1,2,4; Fátima Baltazar^1,2*    

1 -  Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal;

2 - ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal;

3 - Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, São Paulo, Brazil;

4 - Molecular Oncology Research Center, Barretos Cancer Hospital, Pio XII Foundation, Barretos, São Paulo, Brazil;

5 - Department of Orthopedics, Barretos Cancer Hospital, Pio XII Foundation, Barretos, São Paulo, Brazil;

6 - Department of Pathology, Barretos Cancer Hospital, Pio XII Foundation, Barretos, São Paulo, Brazil;

7 - Medical Faculty, UNESP, Botucatu, São Paulo, Brazil;

8 - Centre for Cell Biology and Department of Biology, University of Aveiro, Aveiro, Portugal;

9 - Medical Faculty, University of Porto, Porto, Portugal;

10 - IPATIMUP – Institute of Molecular Pathology and Immunology of University of Porto, Porto, Portugal;

11- Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, Canada.

Abstract:

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.

Revista: Journal of Translational Medicine

Link: http://www.translational-medicine.com/content/12/1/118