title: Toll-like receptors -4 and -5 in oral and cutaneous squamous cell carcinomas.
abstract: BACKGROUND
  Oral squamous cell carcinoma (OSCC) has a worse prognosis than cutaneous squamous cell carcinoma (CSCC). Toll-like receptor- 4 (TLR-4) and TLR-5 are transmembrane proteins that recognize endogenous and microbial agents. Their activation has been connected to cancer invasion.
  
  
  OBJECTIVE
  The aim was to study the expression of TLR-4 and TLR-5 in OSCC and CSCC samples, and the effects of TLR-5 ligand flagellin on the proliferation, migration, and invasion of different mucocutaneous cell lines in vitro.
  
  
  METHODS
  Samples of early-stage tumors (T1-T2N0M0) from 63 patients with OSCC and CSCC were obtained, in addition to eight normal mucosa and skin tissues from healthy subjects. Oral-cavity-derived highly aggressive HSC-3, less invasive SAS, and HPV-transformed benign IHGK as well as C-ha-ras-transformed (HaCat) skin carcinoma II-4 and non-invasive A5 cell lines were used. Flagellin-induced mucocutaneous cell lines were compared by using BrdU-proliferation, scratch migration, and myoma organotypic invasion assays.
  
  
  RESULTS
  TLR-4 expression was similar in OSCC and CSCC tumors. TLR-5 was more abundant in OSCC than in CSCC samples. Flagellin induced the proliferation of SAS, II-4 and A5, migration of IHGK, II-4 and A5, and the invasion of II-4 cells. It had no effect on HSC-3 cells.
  
  
  CONCLUSIONS
  Flagellin, a TLR-5 agonist, induced the migration and invasion of less aggressive mucocutaneous cell lines, but it had no effect on the most invasive oral carcinoma cells. The more aggressive clinical behavior of OSCC compared to CSCC may partially be related to the differences in the expression of TLR-5 in these malignancies.
authors.affiliation: Institute of Dentistry, University of Helsinki, Helsinki, Finland.
authors.forename: Abdirisak Ahmed Haji
authors.initials: AA
authors.lastname: Omar
authors.forename: Johanna
authors.initials: J
authors.lastname: Korvala
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
authors.forename: Susanna
authors.initials: S
authors.lastname: Virolainen
authors.forename: Valtteri
authors.initials: V
authors.lastname: Häyry
authors.forename: Timo
authors.initials: T
authors.lastname: Atula
authors.forename: Risto
authors.initials: R
authors.lastname: Kontio
authors.forename: Jarmo
authors.initials: J
authors.lastname: Rihtniemi
authors.forename: Antti
authors.initials: A
authors.lastname: Pihakari
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D005408:Flagellin / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009924:Organ Culture Techniques; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077195:Squamous Cell Carcinoma of Head and Neck; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D051198:Toll-Like Receptor 5 / Q000819:agonists / Q000096:biosynthesis*
chemical_list: C495345:TLR4 protein, human; C495346:TLR5 protein, human; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D005408:Flagellin
keywords: oral cancer; skin cancer; toll-like receptors