title: Toll-like receptor 3-mediated tumor invasion in head and neck cancer.
abstract: OBJECTIVE
  Chronic inflammation associated with some infectious agents can lead to cancer. The Toll-like receptor (TLR) family is one of the largest and best-studied families of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA and is a major effector of the immune response against viral pathogens.
  
  
  METHODS
  We investigated TLR3 protein expression in 153 oral squamous cell carcinoma (OSCC) specimens using tissue microarray. Furthermore, we used polyinosinic-polycytidylic acid (poly I:C) to stimulate head and neck cancer cells and an inhibitor of endosomal acidification bafilomycin A1 to block the TLR 3 signaling pathway to clarify the role of TLR 3 in OSCC.
  
  
  RESULTS
  Cytoplasmic TLR3 staining was observed in the vast majority of OSCC tissues (73.2%). Strong TLR3 expression was significantly correlated with patients whose tumors were poorly differentiated (P=0.028) and with perineural invasion (P=0.023). Three of the four head and neck cell lines tested (Fadu, OC2, and SCC4) expressed TLR3 mRNA, although at various levels. The stimulation of TLR3-expressing OC2 cells with poly I:C caused the phosphorylation of IFN regulatory factor 3 and IκB and sequentially induced the secretion of interleukin-6 and chemokine (C-C motif) ligand 5 (CCL5) in a dose- and time-dependent manner. Moreover, poly I:C stimulation promoted CCL5-mediated migration in OC2 cells.
  
  
  CONCLUSIONS
  In this report, we provide a novel mechanism for tumor invasion and the TLR3-dependent inflammatory response that could have therapeutic implications for OSCC.
authors: Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Hui-Ching
authors: HC
authors: Chuang
authors: Chao-Cheng
authors: CC
authors: Huang
authors: Chih-Yen
authors: CY
authors: Chien
authors: Jiin-Haur
authors: JH
authors: Chuang
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018946:Chemokine CCL5 / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: D018946:Chemokine CCL5; D020672:I-kappa B Proteins; D050838:Interferon Regulatory Factor-3; D015850:Interleukin-6; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3