Elucidation of chemopreventive mechanisms of mesenchymal stem cells for inflammatory carcinogenesis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460954
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Motoya Masayo 札幌医科大学, 医学部, 助教 (60468080)
• Co-Investigator(Kenkyū-buntansha): Yoshiaki Arimura 札幌医科大学, 医学部, 講師 (80305218) ; Yasuyoshi Naishiro 札幌医科大学, 医療人育成センター, 講師 (80347161)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 間葉系幹細胞 / 発癌 / 化学予防

Outline of Final Research Achievements

MSCs canceled AOM-induced tumor initiation. MSCs inhibited the acute apoptotic response of a genotoxic carcinogen (AARGC) in colonic epithelial cells because of the removal of O6-methylguanine adducts through O6-methylguanine-DNA methyltransferase (Mgmt) activation. However, MSCs did not induce epigenetic Mgmt reactivation. Furthermore, MSCs broadly affected the cell-cycle machinery, leading to G1 arrest. Coculture of IEC-6 intestinal cells with MSCs not only induced G1 arrest, but also apoptosis. The anti-carcinogenetic properties of MSCs required transforming growth factor (TGF)-beta signaling. MSCs inhibited AOM-induced tumor initiation by preventing the initiating cells from sustaining DNA insults and inducing G1 arrest in the initiated cells that escaped from the AARGC. Tumor initiation perturbed by MSCs might potentially dysregulate classical WNT and TGF-beta-Smad signaling pathways.

Free Research Field

消化器内科