Toll-like receptor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases ½

Oncotarget
Chithra Devi PalaniZoya B Kurago

Abstract

Patient treatment for oral squamous cell carcinoma (OSCC) not associated withHuman papillomavirusremains problematic. OSCC microenvironment is typically inflamed and colonized by microorganisms, providing ligands for toll-like receptors (TLR). In immune cells TLR2 and TLR4 activate NF-kB and extracellular signal regulated kinase (ERK)1/2 pathways, leading to upregulation of inhibitory adenosine receptors A2a and A2b, and reduction in stimulatory A1 and A3. How TLR and adenosine receptors function in SCC cells is not understood. To address this gap, we evaluated TLR and adenosine receptor expression and function in human OSCC cells and keratinocytes. TLR2 and A2a were co-expressed in pre-cancer and SCC cells of 17 oral specimens.In vitro, 5/6 OSCC lines expressed more TLR2 than TLR1, 4 or 6 mRNA. TLR2 ligands stimulated A2a expression in TLR2-high cell lines, but no A1 or A3 was detected with or without stimuli. In TLR2-high OSCC, TLR2/1, 2/6 and adenosine receptor agonists activated ERK1/2. TLR2-mediated ERK1/2 phosphorylation resulted in accumulation of c-FOS, ERK-dependent cell proliferation and reduced caspase-3 activity. Similar ERK1/2-dependent proliferation and decreased caspase-3 activity were caused by combined TLR2 and...Continue Reading

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Citations

Mar 20, 2019·Head and Neck Pathology·Joon Koh, Zoya B Kurago
Jan 11, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ranya ElsayedMohammed E Elsalanty
Oct 2, 2020·Biological & Pharmaceutical Bulletin·Guo-Min LiuYun-Gang Luo
Apr 29, 2020·Scientific Reports·Kyla R RodgersRichard C Chou
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Apr 27, 2021·Frontiers in Oncology·Xiaofeng DuanBei Liu

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Methods Mentioned

BETA
xenograft
PCR
dissecting
electrophoresis
Assay

Software Mentioned

Image Lab
GraphPad
Prism
GIMP

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