7-days of FREE Audio papers, translation & more with Prime
7-days of FREE Prime access
7-days of FREE Audio papers, translation & more with Prime
7-days of FREE Prime access
https://doi.org/10.1158/1940-6207.c.6547331
Copy DOIPublication Date: Apr 3, 2023 |
License type: CC BY 4.0 |
<div>Abstract<p>It has been established that COX-2 and downstream signaling by prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) play a key role in tumorigenesis through generation of inflammatory microenvironment. Toll-like receptor (TLR) signaling through myeloid differentiation factor 88 (MyD88) also regulates inflammatory responses in tumors. However, the relationship between these distinct pathways in tumorigenesis is not yet fully understood. We herein investigated the role of MyD88 in gastric tumorigenesis using <i>Gan</i> mice, which develop inflammation-associated gastric tumors due to the simultaneous activation of the COX-2/PGE<sub>2</sub> pathway and Wnt signaling. Notably, the disruption of <i>Myd88</i> in <i>Gan</i> mice resulted in the significant suppression of gastric tumorigenesis with the inhibition of inflammatory responses, even though COX-2/PGE<sub>2</sub> pathway is constitutively activated. Moreover, <i>Myd88</i> disruption in bone marrow–derived cells (BMDCs) in <i>Gan</i> mice also suppressed inflammation and tumorigenesis, indicating that MyD88 signaling in BMDCs regulates the inflammatory microenvironment. We also found that expression of <i>Tlr2</i> and its coreceptor <i>Cd14</i> was induced in tumor epithelial cells in <i>Gan</i> mice, which was suppressed by the disruption of <i>Myd88</i>. It has already been shown that TLR2/CD14 signaling is important for stemness of intestinal epithelial cells. These results indicate that MyD88 in BMDCs, together with COX-2/PGE<sub>2</sub> pathway, plays an essential role in the generation of the inflammatory microenvironment, which may promote tumorigenesis through induction of TLR2/CD14 pathway in tumor epithelial cells. These results suggest that inhibition of TLR/MyD88 signaling together with COX-2/PGE<sub>2</sub> pathway will be an effective preventive strategy for gastric cancer. <i>Cancer Prev Res; 9(3); 253–63. ©2016 AACR</i>.</p></div>
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.