The role of bone marrow-derived cells and interleukin-17 in the mouse model of Helicobacter-infected gastric cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 23590919
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyushu University
• Principal Investigator: TAKAISHI Shigeo 九州大学, 学内共同利用施設等, 准教授 (20596829)
• Research Collaborator: WANG Timothy C. コロンビア大学, 医学部消化器内科, 教授 ; HAYAKAWA Yoku コロンビア大学, 医学部消化器内科, 主任研究員
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: 胃発癌マウス / 胃前庭部上皮幹細胞 / Lgr5陽性細胞 / ガストリン/CCK２受容体 / プロガストリン / ヘリコバクター菌感染 / 発癌物質メチルニトロソウレア / CCK２受容体阻害薬YF476

Outline of Final Research Achievements

We found that gastrin/CCK2-receptor (CCK2R) defines antral stem cells at position +4, which overlapped with an Lgr5 negative or low cell population but was distinct from typical antral Lgr5 high stem cells. Treatment with progastrin interconverts Lgr5 negative or low, CCK2R positive cells into Lgr5 high cells, increases CCK2R positive cell numbers and promotes gland fission and carcinogenesis in response to the chemical carcinogen MNU. Pharmacological inhibition or genetic ablation of CCK2R attenuated progastrin-dependent stem cell expansionand carcinogenesis.
In summary, CCK2R labels +4 antral stem cells that can be activated and expanded by progastrin, thus identifying one hormonal trigger for gastric stem cell interconversion and a potential target for gastric cancer chemoprevention and therapy.

Free Research Field

消化器病態学（消化器癌の発癌機構）