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

Soft tissue sarcomas (STS) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. In the present study, the expression and clinical-pathological significance of monocarboxylate transporters (MCTs), important proteins involved in cancer cells’ metabolic reprogramming, was evaluated in a series of 86 STS. Importantly, an association between MCT expression and poor prognostic variables was observed. Additionally, nuclear expression of MCT1 is described for the first time, being associated with good prognostic variables.

Authors and Affiliations:

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.

Journal: Journal of Translational Medicine

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