title: Toll-like receptors 2, 4, and 9 in primary, metastasized, and recurrent oral tongue squamous cell carcinomas.
abstract: BACKGROUND
  Toll-like receptors (TLRs) are pattern-recognizing proteins involved in innate immunity and they seem to regulate both cancer progression and inhibition. In oral cancer, TLR activation has been linked to invasion. To define the role of TLR-2, TLR-4, and TLR-9 in oral tongue squamous cell carcinoma (OTSCC), we studied their expression in vivo in OTSCC tumor samples, as well as in vitro in cell invasion model.
  
  
  METHODS
  We used immunohistochemistry to compare the expression of TLR-2, TLR-4, and TLR-9 in 21 primary Stage I-II OTSCCs, neck metastases, and recurrent tumors. In addition, we used myoma organotypic invasion assay to evaluate the effect of GIT27 (4,5-dihydro-3-phenyl-5-isoxasoleaceticacid) on the invasion of the HSC-3 OTSCC cell line.
  
  
  RESULTS
  TLR-2, TLR-4, and TLR-9 were expressed in most tumors. Nuclear TLR-2 expression occurred more often in primary tumors than in neck metastases or recurrent tumors of the neck, whereas nuclear TLR-4 expression and cytoplasmic TLR-9 expression were higher in primary tumors than in local recurrent tumors. GIT27 did not affect the invasion of HSC-3 OTSCC cells, but a myoma organotypic invasion assay revealed that the expression of TLR-2 and TLR-4 was stronger in deeper-invading cells.
  
  
  CONCLUSIONS
  TLR-2, TLR-4, and TLR-9 were expressed in primary tumors, neck metastases as well as in recurrent tumors of OTSCC. Thus, these receptors seem to play a role in both the development and progression of tongue carcinoma. These TLRs may also contribute to the invasive potential of OTSCC.
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Mäkinen
authors.affiliation: Institute of Dentistry, Biomedicum 1, University of Helsinki, Helsinki, Finland.
authors.forename: Abdirisak
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Department of Pathology, HUSLAB, Helsinki University Hospital, Helsinki, Finland.|Department of Oral Pathology, Institute of Dentistry, University of Helsinki, Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Lehtonen
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Antti A
authors.initials: AA
authors.lastname: Mäkitie
authors.affiliation: Institute of Dentistry, Biomedicum 1, University of Helsinki, Helsinki, Finland.|Department of Diagnostics and Oral Medicine, Institute of Dentistry, Oulu University Hospital and, University of Oulu, Oulu, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.affiliation: Department of Surgery, Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland.
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Atula
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D010080:Oxazoles / Q000494:pharmacology; D000077195:Squamous Cell Carcinoma of Head and Neck; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis; D051193:Toll-Like Receptors / Q000096:biosynthesis*; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C518641:3-phenyl-4,5-dihydro-5-isoxazole acetic acid; D000085:Acetates; D010080:Oxazoles; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
keywords: Toll-like receptor; head and neck cancer; invasion; oral cancer; oral tongue squamous cell carcinoma