Elevated TLR5 expression in vivo and loss of NF-kappa B activation via TLR5 in vitro detected in HPV-negative oropharyngeal squamous cell carcinoma

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Kylmä , A K , Tolvanen , T A , Carpén , T , Haglund , C , Mäkitie , A , Mattila , P S , Grenman , R , Jouhi , L , Sorsa , T , Lehtonen , S & Hagström , J 2020 , ' Elevated TLR5 expression in vivo and loss of NF-kappa B activation via TLR5 in vitro detected in HPV-negative oropharyngeal squamous cell carcinoma ' , Experimental and Molecular Pathology , vol. 114 , 104435 . https://doi.org/10.1016/j.yexmp.2020.104435

Title: Elevated TLR5 expression in vivo and loss of NF-kappa B activation via TLR5 in vitro detected in HPV-negative oropharyngeal squamous cell carcinoma
Author: Kylmä, Anna Kaisa; Tolvanen, Tuomas Aleksi; Carpén, Timo; Haglund, Caj; Mäkitie, Antti; Mattila, Petri S.; Grenman, Reidar; Jouhi, Lauri; Sorsa, Timo; Lehtonen, Sanna; Hagström, Jaana
Contributor organization: HUSLAB
Department of Pathology
University of Helsinki
Helsinki University Hospital Area
Sanna Lehtonen research group
Research Programs Unit
CAMM - Research Program for Clinical and Molecular Metabolism
HUS Abdominal Center
II kirurgian klinikka
Department of Surgery
CAN-PRO - Translational Cancer Medicine Program
Faculty of Medicine
HUS Head and Neck Center
Department of Ophthalmology and Otorhinolaryngology
Korva-, nenä- ja kurkkutautien klinikka
Clinicum
Department of Oral and Maxillofacial Diseases
Suu- ja leukakirurgian yksikkö
Medicum
Date: 2020-06
Language: eng
Number of pages: 9
Belongs to series: Experimental and Molecular Pathology
ISSN: 0014-4800
DOI: https://doi.org/10.1016/j.yexmp.2020.104435
URI: http://hdl.handle.net/10138/328475
Abstract: In oropharyngeal squamous cell carcinoma (OPSCC), the expression pattern of toll-like receptors (TLRs), in comparison between human papillomavirus (HPV)-positive and -negative tumors differs. TLRs control innate immune responses by activating, among others, the nuclear factor-κΒ (NF-κΒ) signaling pathway. Elevated NF-κΒ activity is detectable in several cancers and regulates cancer development and progression. We studied TLR5 expression in 143 unselected consecutive OPSCC tumors, and its relation to HPV-DNA and p16 status, clinicopathological parameters, and patient outcome, and studied TLR5 stimulation and consecutive NF-κB cascade activation in vitro in two human OPSCC cell lines and immortalized human keratinocytes (HaCat). Clinicopathological data came from hospital registries, and TLR5 immunoexpression was evaluated by immunohistochemistry. Flagellin served to stimulate TLR5 in cultured cells, followed by analysis of the activity of the NF-κB signaling cascade with In-Cell Western for IκΒ and p-IκΒ. High TLR5 expression was associated with poor disease-specific survival in HPV-positive OPSCC, which typically shows low TLR5 immunoexpression. High TLR5 immunoexpression was more common in HPV-negative OPSCC, known for its less-favorable prognosis. In vitro, we detected NF-κΒ cascade activation in the HPV-positive OPSCC cell line and in HaCat cells, but not in the HPV-negative OPSCC cell line. Our results suggest that elevated TLR5 immunoexpression may be related to reduced NF-κΒ activity in HPV-negative OPSCC. The possible prognosis-worsening mechanisms among these high-risk OPSCC patients however, require further evaluation.
Subject: 3111 Biomedicine
Oropharyngeal squamous cell carcinoma
Human papillomavirus
Toll-like receptor
Nuclear factor-κΒ
Nuclear factor-kappa B
CANCER-CELLS
KINASE-ALPHA
SURVIVAL
PROLIFERATION
HUMAN-PAPILLOMAVIRUS
MESENCHYMAL TRANSITION
INTERACTING PROTEIN
INFLAMMATION
TOLL-LIKE RECEPTORS
TNF-ALPHA
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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