Abstract ED01-02: Inflammatory responses in gastrointestinal cancer development and malignant progression Free

Approximately 20% of malignant cancers are associated with chronic infectious disease. Moreover, accumulating evidence has indicated that infection-induced chronic inflammation plays an important role in cancer development. For example, atrophic gastritis and chronic hepatitis caused by H. pylori infection and hepatitis virus infection, respectively, are risk factors for cancer development in the respective organs. Consistently, regular use of non-steroidal anti-inflammatory drugs (NSAIDs) that target cyclooxygenase (COX)-2, reduces a risk of gastrointestinal cancer development. We have constructed gastric cancer mouse model, Gan mice, by transgenic expression of Wnt1, COX-2, and mPGES-1, which activates canonical Wnt signaling and inflammatory COX-2/PGE₂ pathway simultaneously in the stomach. Importantly, Gan mice develop inflammation-associated gastric cancer with 100% incidence. Using Gan mouse model, we have found that bacterial infection through TLR/Myd88 signaling as well as proinflammatory cytokine TNF-α pathway are required for gastric tumor development. Both pathways activate NF-κB in cancer cells, and recent results indicate that NF-κB activation induces dedifferentiation of epithelial cells through acquisition of stem-cell-like properties. Moreover, it has been shown that p53 mutation activates NF-κB pathway in cancer tissues. These results indicate that NF-κB activation caused by cytokine signaling or oncogenic activation plays a key role in gastrointestinal cancer development. Moreover, our preliminary results indicate that inflammatory responses are required also for malignant invasion. Accordingly, regulation of chronic inflammation will be an effective preventive strategy against gastrointestinal cancer development and progression.

Citation Format: Masanobu Oshima. Inflammatory responses in gastrointestinal cancer development and malignant progression. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr ED01-02.