Flagellin promotes the proliferation of gastric cancer cells via the Toll-like receptor 5

Song, Eun-Jung; Kang, Min‐Jung; Kim, Yong-Seok; Kim, Sun-Moon; Lee, Sang-Eok; Kim, Chang-Hwan; Kim, Dong-Jae; Park, Jong‐Hwan

doi:10.3892/ijmm.2011.656

Cited by 38 publications

(34 citation statements)

References 26 publications

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“…Previously, intense links have emerged between inflammation and the initiation and progression of several cancer types, including stomach, breast, ovary and liver (19). Chronic inflammation elicited by certain bacteria, for instance Helicobacter pylori , has been found to promote carcinogenesis (20). Activation of TLRs may favor a contribution for cancer progression and development, however, activation of various TLRs may exhibit contradictory results (21).…”

Section: Discussionmentioning

confidence: 99%

Non-invasive imaging of Toll-like receptor 5 expression using 131I-labeled mAb in the mice bearing H22 tumors

et al. 2014

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Toll-like receptor 5 (TLR5) is overexpressed in several cancers and metastases, and presents an enticing target for molecular imaging of primary tumors. In the present study, 131I-anti-TLR5 monoclonal antibody (mAb) was evaluated for its use as a novel radiotracer for imaging hepatocarcinoma in mice bearing H22 tumors. The expression of TLR5 was analyzed by quantitative polymerase chain reaction and immunohistochemistry. The anti-TLR5 mAb and isotype immunoglobulin G (IgG) were radiolabeled with iodine-131 by the Iodogen method. The in vitro stability of iodinalized probes was determined in serum or saline for a series of times, and then evaluated with radio-thin-layer chromatography. The biodistribution study and autoradiography were performed in H22 tumor-bearing mice. It was found that H22-xenografted tumor tissue exhibited a higher level of TLR5 expression compared with normal liver tissues. 131I-anti-TLR5 mAb and 131I-IgG were obtained subsequent to purification, with high radiochemical purity (>95%), and remained stable for 48 h in human serum. The target-to-non-target ratio in the 131I-anti-TLR5 mAb group was significantly higher compared with the 131I-IgG group. The biodistribution study and autoradiography demonstrated that 131I-anti-TLR5 mAb was specifically retained in hepatocarcinoma with a high tumor uptake. Altogether, these results show that 131I-anti-TLR5 mAb is capable of detecting lesions in a TLR5-expressing tumor, with high target selectivity, and may offer a promising agent for hepatocarcinoma diagnosis and encourage further investigation.

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Section: Discussionmentioning

confidence: 99%

Non-invasive imaging of Toll-like receptor 5 expression using 131I-labeled mAb in the mice bearing H22 tumors

et al. 2014

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“…Interestingly, Chochi et al (104) not only showed that H. pylori augmented the growth of GC via the LPS-TLR4 pathway but also found that this bacterium attenuated the antitumor activity and IFN-γ-mediated cellular immunity of human mononuclear cells. In addition, Song et al (131) have suggested that flagellin-activated TLR5 enhances the proliferation of GC cells through an ERK-dependent pathway. Furthermore, Tye et al (132) have proposed a novel role for TLR2 in promoting gastric tumorigenesis independent of inflammation, whereby up-regulation of TLR2 within epithelial tumor cells, rather than infiltrating inflammatory cells, by the uncontrolled activation of the oncogenic transcription factor STAT3, promoted gastric tumor cell proliferation, and survival via up-regulation of anti-apoptotic genes [e.g., BCL2-related protein A1 ( BCL2A1 ), baculoviral IAP repeat containing 3 ( BIRC3 ), and B-cell CLL/lymphoma 3 ( BCL3 )].…”

Section: Toll-like Receptors and Helicobacter Pylori-related Gastric mentioning

confidence: 99%

Pattern-Recognition Receptors and Gastric Cancer

2014

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Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy.

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“…For example, TLR5 is highly expressed in breast carcinoma and gastric carcinoma cells, and TLR5 signaling inhibits breast cancer growth, but promotes the proliferation of gastric cancer cells. [9,12,19] However, it is not all the TLRs expressed in cancer cells are functional to induce inflammatory response. In breast cancer cell MDA-MB-231 and MDA-MB-435, TLR5 is abnormally localized only in cytoplasm, so NF-κB signaling cannot be activated by TLR5 agonist in these cells.…”

Section: Resultsmentioning

confidence: 99%

Application potential of toll-like receptors in cancer immunotherapy

Shi

Chen

et al. 2016

Medicine

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Toll-like receptors (TLRs), as the most important pattern recognition receptors in innate immunity, play a pivotal role in inducing immune response through recognition of microbial invaders or specific agonists. Recent studies have suggested that TLRs could serve as important regulators in the development of a variety of cancer. However, increasing evidences have shown that TLRs may display quite opposite outcomes in cancer development. Although several potential therapeutic Toll-like receptor ligands have been found, the mechanism and therapy prospect of TLRs in cancer development has to be further elucidated to accelerate the clinical application. By performing a systematic review of the present findings on TLRs in cancer immunology, we attempted to evaluate the therapeutic potential of TLRs in cancer therapy and elucidate the potential mechanism of cancer progress regulated by TLR signaling and the reported targets on TLRs for clinical application. An electronic databases search was conducted in PubMed, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database from their inception to February 1, 2016. The following keywords were used to search the databases: Toll-like receptors, cancer therapy, therapeutic target, innate immunity. Of 244 studies that were identified, 97 nonrelevant studies were excluded. In total, 147 full-text articles were assessed, and from these, 54 were excluded as they did not provide complete key information. Thus, 93 studies were considered eligible and included in the analysis. According to the data from the included trials, 14 TLR ligands (77.8%) from 82 studies have been demonstrated to display antitumor property in various cancers, whereas 4 ligands (22.2%) from 11 studies promote tumors. Among them, only 3 TLR ligands have been approved for cancer therapy, and 9 ligands were in clinical trials. In addition, the potential mechanism of recently reported targets on TLRs for clinical application was also evaluated in this review. We show that targeting TLRs in cancer immunotherapy is a promising strategy for cancer therapy, and the specific TLR ligands, either alone or combination, exhibit antitumor potential.

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Flagellin promotes the proliferation of gastric cancer cells via the Toll-like receptor 5

Cited by 38 publications

References 26 publications

Non-invasive imaging of Toll-like receptor 5 expression using 131I-labeled mAb in the mice bearing H22 tumors

Non-invasive imaging of Toll-like receptor 5 expression using 131I-labeled mAb in the mice bearing H22 tumors

Pattern-Recognition Receptors and Gastric Cancer

Application potential of toll-like receptors in cancer immunotherapy

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