title: Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization.
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.
authors.forename: Céline
authors.initials: C
authors.lastname: Pinheiro
authors.forename: Valter
authors.initials: V
authors.lastname: Penna
authors.forename: Filipa
authors.initials: F
authors.lastname: Morais-Santos
authors.forename: Lucas F
authors.initials: LF
authors.lastname: Abrahão-Machado
authors.forename: Guilherme
authors.initials: G
authors.lastname: Ribeiro
authors.forename: Emílio C
authors.initials: EC
authors.lastname: Curcelli
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Olivieri
authors.forename: Sandra
authors.initials: S
authors.lastname: Morini
authors.forename: Isabel
authors.initials: I
authors.lastname: Valença
authors.forename: Daniela
authors.initials: D
authors.lastname: Ribeiro
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Schmitt
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4710-057 Braga, Portugal. fbaltazar@ecsaude.uminho.pt.
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
mesh_terms: D006801:Humans; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D011379:Prognosis; D012509:Sarcoma / Q000378:metabolism* / Q000503:physiopathology; D013347:Subcellular Fractions / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D027501:Monocarboxylic Acid Transporters