title: Toll-like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue.
abstract: BACKGROUND
  Toll-like receptor 9 (TLR9) is a cellular receptor, which recognizes bacterial and host-derived DNA. Stimulation of TLR9 induces cellular invasion via matrix metalloproteinase 13 (MMP-13). The aim of this study was to evaluate the role of TLR9 in invasion of oral tongue squamous cell carcinoma (OTSCC).
  
  
  METHODS
  The effects of TLR9 ligands on oral squamous cell carcinoma cell lines were studied with invasion and migration assays, as well as in a myoma organotypic model.
  
  
  RESULTS
  The TLR9 ligand, CpG-ODN, increased invasion and migration in OTSCC lines. These effects were reduced by TLR9 siRNA or inhibition with TLR9 antibodies. Immunohistochemical analysis of tissues from 195 patients with OTSCC revealed that TLR9 was expressed in 181/195 carcinomas. The expression of TLR9 was higher in the malignant cells than in the normal epithelium. High TLR9 expression was associated with high MMP-13 expression and poor differentiation. High TLR9 expression was also identified as an independent predictor of poor prognosis (HR 1.810, 95% CI [1.053-3.112]).
  
  
  CONCLUSIONS
  Toll-like receptor 9 mediates OTSCC invasion and migration in vitro and is an independent prognostic factor of OTSCC. Inhibition of TLR9 may be a novel therapeutic opportunity in oral cancer.
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland.|Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Joonas H
authors.initials: JH
authors.lastname: Kauppila
authors.affiliation: Medical Research Center Oulu, Oulu, Finland.|Department of Dentistry, University of Oulu, Oulu, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Korvala
authors.affiliation: Department of Dentistry, University of Oulu, Oulu, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Siirilä
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland.
authors.forename: Marika
authors.initials: M
authors.lastname: Manni
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, University of Helsinki, Helsinki, Finland.|Department of Otorhinolaryngology and Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Mäkinen
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Huslab, Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, University of Helsinki, Helsinki, Finland.|Department of Otorhinolaryngology and Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Atula
authors.affiliation: Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland.
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Katri S
authors.initials: KS
authors.lastname: Selander
authors.affiliation: Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
authors.affiliation: Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.|Anatomy and Cell biology, University of Oulu, Oulu, Finland.
authors.forename: Petri P
authors.initials: PP
authors.lastname: Lehenkari
authors.affiliation: Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.|Department of Dentistry, University of Oulu, Oulu, Finland.|Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011379:Prognosis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis* / Q000235:genetics; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D034741:RNA, Small Interfering; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D053509:Matrix Metalloproteinase 13
keywords: Toll-like receptor 9; invasion; matrix metalloproteinase 13; migration; tongue cancer