Role of IL-33 on gastric cancer development -Analysis using new model mice-

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670191
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Shinshu University
• Principal Investigator: NAKAYAMA Jun 信州大学, 学術研究院医学系, 教授 (10221459)
• Co-Investigator(Kenkyū-buntansha): KAKUTA Shigeru 東京大学, 農学生命科学研究科, 准教授 (80345032) ; TAKAMOTO Masaya 信州大学, 医学部, 特任教授 (90226928) ; KAWAKUBO Masatomo 信州大学, 学術研究院医学系, 助教 (70397305)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 胃癌 / 糖鎖 / 炎症 / サイトカイン / ダブルノックアウトマウス / ゲノム編集

Outline of Final Research Achievements

A4gnt knockout (KO) mouse is a unique model for studying gastric cancer pathogenesis. Extensive gene analysis for gastric mucosa of A4gnt KO mouse indicated possible involvement of IL-33/ST2 axis in gastric cancer development. Aim of this study is to clarify the role of IL-33/ST2 axis on pathogenesis of gastric cancer. To this end, we generated A4gnt/Il1rl1 double KO mice by crossing A4gnt KO mice and Il1rl1 KO mice that deficient in ST2, and then compared A4gnt/Il1rl1 DKO mice with A4gnt KO mice at 10 weeks of age (n = 6). Obvious difference was not found in gastric pathology. However, real-time PCR analysis revealed that expression levels of Il33, Fgf7, Ccl2, Grem1 and Arg1 in A4gnt/Il1rl1 DKO mice were significantly reduced compared to A4gnt KO mice, suggesting that IL-33/ST2 axis regulates tumor-promoting inflammation in A4gnt KO mice.

Free Research Field

病理学