title: A reverse Warburg metabolism in oral squamous cell carcinoma is not dependent upon myofibroblasts.
abstract: BACKGROUND
  The reverse Warburg effect describes the phenomenon that epithelial cancer cells take advantage of the metabolic machinery from nearby cancer-associated fibroblast, inducing them to produce lactate and ketones to fuel the high metabolic demands of the epithelial tumour tissues. This is in breast cancer observed as a lack of stromal caveolin-1 (CAV-1) and an increased expression of monocarboxylate transporter 4 (MCT-4) in the tumour stroma, with a concomitant increase in the expression of monocarboxylate transporter 1 (MCT-1) in the epithelial, tumour compartment. The lack of CAV-1 and increased expression of MCT-4 have been shown to have prognostic importance, primarily in patients with breast cancer. However, this phenomenon has only scarcely been described in oral squamous cell carcinoma (OSCC). Given the prognostic importance of myofibroblasts in OSCC, we also examined a potential relationship between the expression of MCT-4 and the presence of myofibroblasts.
  
  
  METHODS
  Paraffin-embedded tissues from 30 patients with OSCC were immunostained with antibodies towards MCT-1, MCT-4, Cav-1, GLUT-1, α-SMA, TOMM20 and KI-67, and evaluated for their specific epithelial and stromal expression.
  
  
  CONCLUSIONS
  In patients with OSCC, we find an increased expression of MCT-1 and MCT-4 in both the epithelial and stromal compartment, with almost no overlap in their spatial expression. We found a large spatial overlap between α-SMA and MCT-1 in the stroma compartment, but no relationship between MCT-4 and myofibroblasts. Interestingly, we did not observe any relationship between the absence of CAV-1 and the presence of MCT-4 as has been shown in breast carcinomas.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: David H
authors.initials: DH
authors.lastname: Jensen
authors.affiliation: Department of Pathology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marianne H
authors.initials: MH
authors.lastname: Therkildsen
authors.affiliation: Department of Oral Health Sciences, Faculty of Health Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Erik
authors.initials: E
authors.lastname: Dabelsteen
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D051242:Caveolin 1 / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000276:immunology / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009124:Muscle Proteins / Q000276:immunology / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D011817:Rabbits; D000077195:Squamous Cell Carcinoma of Head and Neck; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000199:Actins; D051242:Caveolin 1; D051272:Glucose Transporter Type 1; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C541116:ACTA2 protein, human; C406962:SLC16A4 protein, human
keywords: myofibroblast; oral squamous cell carcinoma; reverse Warburg effect