Establishment and application of animal model of liver cancer stem cell using induced pluripotent stem cells
| Project/Area Number |
16K07116
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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 |
Tumor biology
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
笠井 智成 東京工科大学, 応用生物学部, 准教授 (30530191)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肝がん / がん幹細胞 / 実験動物モデル / 人工多能性幹細胞 / 肝がん幹細胞 / 動物モデル |
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| Outline of Final Research Achievements |
Cancer stem cells were induced from mouse iPS cells by culturing in the presence of conditioned medium prepared from human hepatoma cell lines using a method that we have established. The cancer stem cells exhibited high tumorigenicity with rapid growth in immunodeficient mice. Primary cultured cells derived from this tumor were induced to differentiate into hepatocytes by a series of growth factors to produce liver cancer stem cell-like cells. Tumors formed by directly transplanting these cells into the livers of immunodeficient mice showed markers specific to liver cancer cells and also expression of factors related to stemness. However, only a part of tumors show differentiation to hepatocyte lineage, and it is necessary to establish more efficient animal models of liver cancer stem cells for detailed analysis of these cells.
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| Academic Significance and Societal Importance of the Research Achievements |
進行肝がんの化学療法や放射線治療に対する治療抵抗性の原因としてのがん幹細胞の存在と、それを標的とした治療法の開発が注目されている。しかし、がん幹細胞をがん組織検体から分離して長期に維持することが難しく、そのため、がん幹細胞の詳しい解析は従来困難であった。本研究では、遺伝子操作を用いることなく、より自然な条件下で肝がん幹細胞モデルを作製することが出来た。さらに、iPS細胞を出発材料とすることから、種々の遺伝的背景を持つ試料の安定供給が可能となった。今後、より効率的な動物モデル作製法の開発により、がん幹細胞の詳細な病態解析及び薬剤耐性機序の解明に基づいた創薬が期待される。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Up-Regulation of PI 3-Kinases and the Activation of PI3K-Akt Signaling Pathway in Cancer Stem-Like Cells Through DNA Hypomethylation Mediated by the Cancer Microenvironment2018
Author(s)
Oo AKK, Calle AS, Nair N, Mahmud H, Vaidyanath A, Yamauchi J, Khayrani AC, Du J, Alam MJ, Seno A, Mizutani A, Murakami H, Iwasaki Y, Chen L, Kasai T, Seno M
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Journal Title
Transl Oncol
Volume: 11
Issue: 3
Pages: 653-663
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment2017
Author(s)
Neha Nair, Anna Sanchez Calle, Maram Hussein Zahra, Marta Prieto-Vila, Aung Ko Ko Oo, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Junko Masuda, Yoshiaki Iwasaki, Hiromi Tanaka, Tomonari Kasai, Masaharu Seno
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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