The establishment of new therapy targeting metabolic characteristics and cancer-stroma interaction for pancreatic cancer
| Project/Area Number |
15K09055
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tohoku Medical and Pharmaceutical University (2017-2018)
Miyagi Prefectural Hospital Organization Miyagi Cancer Center (2015-2016) |
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Principal Investigator |
SATOH Kennichi 東北医科薬科大学, 医学部, 教授 (10282055)
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| Research Collaborator |
YOKOYAMA Misa
SHIBUYA Rie
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 膵癌 / 癌幹細胞 / ピルビン酸キナーゼ / ペリオスチン / 癌代謝 / 代謝 / PKM2 / Periostin |
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| 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 cells’ gene expression profile by microarray analysis. We analyzed the cells’ energy-producing pathways by XFe Extracellular Flux Analyzers, and detected intracellular metabolites by a capillary electrophoresis time-of-flight mass spectrometer.
We found that 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. Microarray analysis revealed functional association between PKM2 and expression of genes that drive the cell cycle. These results demonstrate that PKM2 play important role for metabolic activities as well as malignancy of PDAC cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，膵臓癌の新たな治療標的としてPKM2に着目した。PKM2は代謝を介し，遺伝子発現や細胞増殖など膵臓癌の進展に大きく関与していることを明らかにした。さらに、PKM2発現抑制によるスペルミン産生低下について明らかにした。これらの結果はPKM2を標的とした新しい膵癌治療法の開発の可能性を示唆するものである。予後の非常に悪い膵癌に対する新し治療法開発の可能性を示したことは、社会的に大きな意義を持つ。
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Report
(5 results)
Research Products
(4 results)
