TLR7 and TLR8 expression increases tumor cell proliferation and promotes chemoresistance in human pancreatic cancer

  • Chronic inflammation as an important epigenetic and environmental factor for putative tumorigenesis and tumor progression may be associated with specific activation of Toll-like receptors (TLR). Recently, carcinogenesis has been suggested to be dependent on TLR7 signaling. In the present study, we determined the role of both TLR7 and TLR8 expression and signaling in tumor cell proliferation and chemoresistance in pancreatic cancer. Expression of TLR7/TLR8 in UICC stage I-IV pancreatic cancer, chronic pancreatitis, normal pancreatic tissue and human pancreatic (PANC1) cancer cell line was examined. For in vitro/in vivo studies TLR7/TLR8 overexpressing PANC1 cell lines were generated and analyzed for effects of (un-)stimulated TLR expression on tumor cell proliferation and chemoresistance. TLR expression was increased in pancreatic cancer, with stage-dependent upregulation in advanced tumors, compared to earlier stages and chronic pancreatitis. Stimulation of TLR7/TLR8 overexpressing PANC1 cells resulted in elevated NF-κB and COX-2 expression, increased cancer cell proliferation and reduced chemosensitivity. More importantly, TLR7/TLR8 expression increased tumor growth in vivo. Our data demonstrate a stage-dependent upregulation of both TLR7 and TLR8 expression in pancreatic cancer. Functional analysis in human pancreatic cancer cells point to a significant role of both TLRs in chronic inflammation-mediated TLR7/TLR8 signaling leading to tumor cell proliferation and chemoresistance.

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Author:Tanja Grimmig, Niels Matthes, Katharina Hoeland, Sudipta Tripathi, Anil Chandraker, Martin Grimm, Romana Mönch, Eva-Maria Moll, Helmut Friess, Igor TsaurORCiDGND, Roman A. BlahetaORCiD, Cristoph T. Germer, Ana Maria da Silva Rosa Waaga, Martin Gasser
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Parent Title (English):International journal of oncology
Publisher:Spandidos Publ.
Place of publication:Athens
Document Type:Article
Year of Completion:2015
Date of first Publication:2015/07/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/07/11
Tag:TLR7; TLR8; agonists; inflammation; pancreatic cancer
Page Number:10
First Page:857
Last Page:866
Copyright: © Grimmig et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0