| セッション情報 |
The 2nd JSGE International Topic Conference
3）Gastric Cancer；From the View of Helicobacter pylori-related Inflammation
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| タイトル |
IT3-4：The Role of Inflammatory Responses in Promotion of Gastric Tumorigenesis
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| 演者 |
Oshima Masanobu（Division of Genetics, Cancer Research Institute, Kanazawa University, Japan） |
| 共同演者 |
Ishikawa Tomo-o（Division of Genetics, Cancer Research Institute, Kanazawa University, Japan）, Oshima Hiroko（Division of Genetics, Cancer Research Institute, Kanazawa University, Japan） |
| 抄録 |
Accumulating evidence has suggested that inflammatory responses play an important role in cancer development, and Helicobacter pylori infection is tightly associated with gastric cancer development. It has been shown that H. pylori infection induces expression of cyclooxygenase-2（COX-2）, which further plays a role in chronic gastritis and gastric tumorigenesis. However, molecular mechanisms of COX-2-related inflammation in gastric carcinogenesis have not been fully understood yet. We have constructed gastric cancer model mice that develop gastric cancer caused by transgenic expression of Wnt1, COX-2, and mPGES-1. Expression of these genes results in simultaneous activation of oncogenic Wnt signaling and inflammatory COX-2/PGE2 pathway in gastric mucosa. It has been shown that proinflammatory cytokine TNF-α promotes development of several types of cancers including liver cancer and ovarian cancer. We thus crossed gastric cancer model mice（Gan mice）with TNF-α gene（Tnf）knockout mice to examine the role of TNF-α in gastric tumorigenesis. Importantly, gastric tumorigenesis was significantly suppressed in Tnf-/- Gan mice, while tumor phenotype was rescued by bone marrow transplantation from wild-type mice. Accordingly, it is possible that TNF-α derived from bone marrow-derived cells is an important tumor-promoting factor for gastric cancer development in the inflammatory microenvironment. By microarray analyses, we found that several genes induced in tumor epithelial cells by TNF-α are important for maintenance of tumorigenicity of gastric cancer cells. It is therefore possible that inhibition of these gene products will be an effective therapeutic and preventive strategy against inflammation-associated gastric cancer. |
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