The establishment of human ex vivo model for the carcinogenesis of IBD associated cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06654
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hibiya Shuji 東京医科歯科大学, 医学部附属病院, 特任助教 (20801963)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: IBD付随がん / 発がん体外モデル / ヒト大腸オルガノイド / 上皮細胞機能不全

Outline of Final Research Achievements

It is well known that the patients with inflammatory bowel disease (IBD) particularly ulcerative colitis (UC) have an increased risk for colon cancer during long-term disease duration. Moreover, IBD related cancer has higher malignant potential that sporadic colon cancer, resulting in intractable cancer. However, the mechanism for carcinogenesis of IBD related cancer remains unknown. We therefore establish in vitro culture system using human colonic organoids to mimic the process of IBD related carcinogenesis. Finally, we found that colonic epithelial cells were transformed by long-term inflammation. We also identified key molecule correlated with carcinogenesis.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

長期間の病歴となるIBD患者では一旦寛解となるも長期間の観察にて癌が発生することから、炎症が沈静化しても上皮細胞は過剰応答状態にある可能性が高いと思われます。我々は炎症応答の蓄積が、がん化の根源と考えその機構を解明することによりIBD付随発がんの予防や一度過剰応答となった細胞をリセットするという新しいがん治療の基盤となることが期待されます。