| 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
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | 間葉系幹細胞 / 発癌 / 化学予防 / 骨髄間葉系幹細胞 / chemoprevention / azoxymethane (AOM) 関連発癌 |
|---|
| 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.
|
