Premium
Toll‐like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue
Author(s) -
Kauppila Joonas H.,
Korvala Johanna,
Siirilä Kristiina,
Manni Marika,
Mäkinen Laura K.,
Hagström Jaana,
Atula Timo,
Haglund Caj,
Selander Katri S.,
Saarnio Juha,
Karttunen Tuomo J.,
Lehenkari Petri P.,
Salo Tuula
Publication year - 2015
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12272
Subject(s) - cancer research , receptor , toll like receptor , biology , cell , cell culture , pathology , medicine , innate immune system , biochemistry , genetics
Background Toll‐like receptor 9 ( TLR 9) is a cellular receptor, which recognizes bacterial and host‐derived DNA . Stimulation of TLR 9 induces cellular invasion via matrix metalloproteinase 13 ( MMP ‐13). The aim of this study was to evaluate the role of TLR 9 in invasion of oral tongue squamous cell carcinoma ( OTSCC ). Methods The effects of TLR 9 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 TLR 9 ligand, CpG‐ ODN , increased invasion and migration in OTSCC lines. These effects were reduced by TLR 9 si RNA or inhibition with TLR 9 antibodies. Immunohistochemical analysis of tissues from 195 patients with OTSCC revealed that TLR 9 was expressed in 181/195 carcinomas. The expression of TLR 9 was higher in the malignant cells than in the normal epithelium. High TLR 9 expression was associated with high MMP ‐13 expression and poor differentiation. High TLR 9 expression was also identified as an independent predictor of poor prognosis ( HR 1.810, 95% CI [1.053–3.112]). Conclusion Toll‐like receptor 9 mediates OTSCC invasion and migration in vitro and is an independent prognostic factor of OTSCC . Inhibition of TLR 9 may be a novel therapeutic opportunity in oral cancer.