TY - JOUR AB - Toll‑like receptor 4 (TLR4), a key regulator of the innate immune system, is expressed not only in immune cells, but also in a number of cancer cells. A biological role for TLR4 in cutaneous squamous cell carcinoma (SCC), however, is unclear. In this study, we first examined TLR4 expression and localization in cases of SCC, actinic keratosis (AK) and Bowen's disease (BD) by immunohistochemistry. TLR4 expression was significantly higher in the SCC than in the AK or BD tissues. We then determined the TLR4 expression level in vivo, in 3 histological subtypes of SCC. TLR4 expression in poorly differentiated SCC was significantly lower compared with that of the moderately and well‑differentiated type. In addition, the CD44 immunoreactivity tended to be high in the cell membrane of poorly differentiated SCC. Of note, poorly differentiated SCC is a risk factor of unfavorable outcomes in affected patients. We then assessed the biological role of TLR4 in HSC‑1 and HSC‑5 SCC cells and HaCaT human keratinocytes. TLR4 knockdown by transfection with siRNA accelerated HSC‑1 and HaCaT cell migration and invasion compared to the control siRNA‑transfected cells. TLR4 knockdown resulted in an increased CD44 expression and in an enhanced filopodia protrusion formation, particularly in HSC‑1. On the whole, these results suggest that a reduced TLR4 expression enhances the malignant features in SCC cases and cultured SCC cell lines. TLR4 may thus play an anti‑tumor role in cutaneous SCC. AD - Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113‑8603, Japan Department of Diagnostic Pathology, Nippon Medical School Musashikosugi Hospital, Kawasaki, Kanagawa 211‑8533, Japan Department of Dermatology, Nippon Medical School, Tokyo 113‑8603, Japan AU - Mikami,Erina AU - Kudo,Mitsuhiro AU - Ohashi,Ryuji AU - Kawahara,Kiyoko AU - Kawamoto,Yoko AU - Teduka,Kiyoshi AU - Fujii,Takenori AU - Kitamura,Taeko AU - Kure,Shoko AU - Ishino,Kousuke AU - Sakatani,Takashi AU - Wada,Ryuichi AU - Saeki,Hidehisa AU - Naito,Zenya DA - 2019/06/01 DO - 10.3892/ijo.2019.4790 EP - 2188 IS - 6 JO - Int J Oncol KW - Toll‑like receptor 4 cutaneous squamous cell carcinoma differentiation CD44 migration invasion filopodia PY - 2019 SN - 1019-6439 1791-2423 SP - 2179 ST - Toll‑like receptor 4 plays a tumor‑suppressive role in cutaneous squamous cell carcinoma T2 - International Journal of Oncology TI - Toll‑like receptor 4 plays a tumor‑suppressive role in cutaneous squamous cell carcinoma UR - https://doi.org/10.3892/ijo.2019.4790 VL - 54 ER -