2015
DOI: 10.3892/ijo.2015.3069
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TLR7 and TLR8 expression increases tumor cell proliferation and promotes chemoresistance in human pancreatic cancer

Abstract: 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 pancreati… Show more

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Cited by 75 publications
(65 citation statements)
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“…Recently, enhanced expression of TLRs has been described in a variety of different tumor entities and depending on the cancer type, could be linked to either favorable or poor prognosis [7,8,9,10,11]. TLR3 and -4 were identified as predictors of poor survival in breast cancer, whereas high TLR9 predicted enhanced survival [12,13].…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Recently, enhanced expression of TLRs has been described in a variety of different tumor entities and depending on the cancer type, could be linked to either favorable or poor prognosis [7,8,9,10,11]. TLR3 and -4 were identified as predictors of poor survival in breast cancer, whereas high TLR9 predicted enhanced survival [12,13].…”
Section: Introductionmentioning
confidence: 99%
“…Additionally, TLR ligation is related to adhesion and metastasis in human colorectal cancer cells and migration in human glioblastoma (via TLR4) and human breast cancer cells (via TLR2) [18,20,21]. Previously, we showed that TLR7 or -8 expression is associated with UICC stage in PDAC and stimulation increases tumor cell proliferation and resistance to the cytostatic agent 5-fluorouracil (5-FU) in pancreatic cancer cells [8]. …”
Section: Introductionmentioning
confidence: 99%
“…However, both observations are not necessarily contradictory because the read-out used by the two teams differed. In a mouse model of pancreatic carcinoma and in humans, two studies demonstrated a role for TLR7 expressed by tumor cells in promoting tumor progression (Grimmig et al, 2015;Ochi et al, 2012). However, one study reported a potential anti-tumoral role of TLR7, although this study was performed in vitro with pancreatic cell lines: the authors demonstrated that TLR7 ligation on tumor cells enhanced lysis by ␥/␦ T cells but did not check for long-term tumor cell proliferation or survival.…”
Section: Controversiesmentioning
confidence: 94%
“…In pancreatic cancer, a strong TLR7 expression by tumor cells compared to the healthy tissue was described in patients as well as in mice model. Furthermore, TLR7 stimulation accelerated tumor progression with increased fibrosis, inflammation and proliferation; decreased the expression of antitumoral molecules such as p16, PTEN, and cyclin D1; and increased that of pro-tumoral molecules such as p53, p21, p27, TGF-␤, peroxisome proliferator-activated receptor ␥, cyclin B1, c-Myc and Src homology protein tyrosine phosphatase 1 (Grimmig et al, 2015;Ochi et al, 2012).…”
Section: Anti-tumoral Effectmentioning
confidence: 99%
“…This explains why tumors occur predominantly among aged humans (Huguley, 1999;Newschaffer, 2001). Current theory of oncogenesis links the existence of cancer genes known as oncogenes to carcinogenesis and in their normal forms; protoncogenes pose no problems (Grimmig et al, 2015). However, in mutated forms, they behave uncontrollably in tissue function and tissue formation.…”
Section: Causes Of Cancermentioning
confidence: 99%