Myeloid Differentiation Factor 88 Signaling in Bone Marrow-Derived Cells Promotes Gastric Tumorigenesis by Generation of Inflammatory Microenvironment

Cancer Prevention Research
Yusuke MaedaMasanobu Oshima

Abstract

It has been established that COX-2 and downstream signaling by prostaglandin E2 (PGE2) 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 Gan mice, which develop inflammation-associated gastric tumors due to the simultaneous activation of the COX-2/PGE2 pathway and Wnt signaling. Notably, the disruption of Myd88 in Gan mice resulted in the significant suppression of gastric tumorigenesis with the inhibition of inflammatory responses, even though COX-2/PGE2 pathway is constitutively activated. Moreover, Myd88 disruption in bone marrow-derived cells (BMDCs) in Gan mice also suppressed inflammation and tumorigenesis, indicating that MyD88 signaling in BMDCs regulates the inflammatory microenvironment. We also found that expression of Tlr2 and its coreceptor Cd14 was induced in tumor epithelial cells in Gan mice, which was suppressed by the disruption of Myd88. It has already been shown that T...Continue Reading

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Citations

Sep 20, 2016·Cellular and Molecular Gastroenterology and Hepatology·Spencer G Willet, Jason C Mills
Mar 14, 2019·Journal of Immunology Research·Lorena Elena MelițMaria Oana Mărginean
Dec 5, 2019·Arquivos De Gastroenterologia·Michele Fernandes RodriguesSônia Maria Neumann Cupolilo
Mar 31, 2017·Oncology Letters·Xiao-Ying ZhangMourad A M Aboul-Soud

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