| Project/Area Number |
18K07981
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53010:Gastroenterology-related
|
|---|
| Research Institution | Tohoku Medical and Pharmaceutical University |
|---|
Principal Investigator |
SATOH Kennichi 東北医科薬科大学, 医学部, 教授 (10282055)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 膵癌 / 癌間質相互作用 / 癌幹細胞 / 癌間質 / PKM" / Periostin |
|---|
| Outline of Final Research Achievements |
To examine PKM2’s expression and role in pancreatic ductal adenocarcinoma(PDAC), we knocked PKM2 down in PDAC cells by introducing small interfering and short hairpin RNAs, and examined the role of this gene in PDAC. We analyzed the cells’energy-producing pathways by Extracellular Flux Analyzers, and detected intracellular metabolites by a capillary electrophoresis time-of-flight mass spectrometer. RNAi-mediated knockdown of PKM2 diminished proliferation, migration, and tumorigenicity of PDAC cell-lines. PKM2 knockdown also resulted in lower glycolytic activities, and decreased levels of some intracellular metabolites such as pyruvate and polyamine but elevated levels of reactive oxygen species. In a syngenic implantation model, murine Ex3LL lung-cancer cells formed smaller tumor nodules in periostin-/- mice than in periostin+/+ mice at metastatic lung sites, suggesting that periostin plays an important role in cancer metastasis.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究では進行膵癌の新たな治療標的として癌間質相互作用と癌組織の多様性に着目した。また、癌間質相互作用と癌組織の多様性に関わる重要な分子としてそれぞれ、PKM2とPeriostinに焦点を絞った。PKM2は膵癌特有の代謝を制御し、膵癌の進展に関与していることが明らかとなった。また、PKM2の下流にスペルミンが存在することも明らかとなり、新しい治療標的分子となる可能性が示唆された。さらにPeriostinも膵癌進展に関与していること、癌の転移に関与していることも明らかにした。これらの知見は、いまだに予後不良である膵癌に対する新しい治療法の開発につながる可能性を持ち、社会的に大きな意義を持つ。
|
