TY  - JOUR
A1  - Grimmig, Tanja
A1  - Matthes, Niels
A1  - Hoeland, Katharina
A1  - Tripathi, Sudipta
A1  - Chandraker, Anil
A1  - Grimm, Martin
A1  - Mönch, Romana
A1  - Moll, Eva-Maria
A1  - Friess, Helmut
A1  - Tsaur, Igor
A1  - Blaheta, Roman A.
A1  - Germer, Cristoph T.
A1  - Waaga, Ana Maria da Silva Rosa
A1  - Gasser, Martin
T1  - TLR7 and TLR8 expression increases tumor cell proliferation and promotes chemoresistance in human pancreatic cancer
T2  - International journal of oncology
N2  - 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.
KW  - TLR7
KW  - TLR8
KW  - pancreatic cancer
KW  - inflammation
KW  - agonists
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50650
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-506508
SN  - 1791-2423
SN  - 1019-6439
N1  - Copyright: © Grimmig et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
VL  - 47
IS  - 3
SP  - 857
EP  - 866
PB  - Spandidos Publ.
CY  - Athens
ER  -