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

Autor: Antti Mäkitie, Petri S. Mattila, Reidar Grénman, Tuomas Aleksi Tolvanen, Lauri Jouhi, Jaana Hagström, Anna Kaisa Kylmä, Timo Carpén, Caj Haglund, Sanna Lehtonen, Timo Sorsa
Přispěvatelé: 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
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Clinical Biochemistry
Nuclear factor-kappa B
0302 clinical medicine
Medicine
Receptor
Oropharyngeal squamous cell carcinoma
Papillomaviridae
Toll-like receptor
PROLIFERATION
NF-kappa B
Middle Aged
Prognosis
TNF-ALPHA
Immunohistochemistry
3. Good health
Gene Expression Regulation
Neoplastic
Oropharyngeal Neoplasms
030220 oncology & carcinogenesis
SURVIVAL
Carcinoma
Squamous Cell
Female
Tumor necrosis factor alpha
Signal transduction
Human papillomavirus
Disease-Free Survival
Pathology and Forensic Medicine
03 medical and health sciences
INFLAMMATION
Humans
CANCER-CELLS
INTERACTING PROTEIN
Molecular Biology
TOLL-LIKE RECEPTORS
MESENCHYMAL TRANSITION
business.industry
HUMAN-PAPILLOMAVIRUS
Papillomavirus Infections
Transcription Factor RelA
Toll-Like Receptor 5
HaCaT
030104 developmental biology
TLR5
Cancer cell
Cancer research
3111 Biomedicine
KINASE-ALPHA
Nuclear factor-κΒ
business
Zdroj: Experimental and Molecular Pathology. 114:104435
ISSN: 0014-4800
Popis: 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.
Databáze: OpenAIRE
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