Live imaging of human pancreatic cancer stem cell dynamics
Project/Area Number |
19K22619
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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Research Institution | Kyoto University |
Principal Investigator |
Seno Hiroshi 京都大学, 医学研究科, 教授 (90335266)
|
Project Period (FY) |
2019-06-28 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | 膵臓 / 難治がん / がん / 癌 |
Outline of Research at the Start |
本研究では、独自の生体「内外」ヒト膵がん実験系を用い、がん幹細胞を頂点とするヒト膵がん組織の動態を可視化する。すなわち、充実したヒト膵がんオルガノイド・ライブラリーをもとに、細胞系譜解析と二光子顕微鏡により、膵がん幹細胞の動態を可視化する。また、ヒト膵がんxenograftにおける膵がん幹細胞動態を、独自のイメージング・ウィンドウ越しに解析する。最後に、生体「内外」モデルの双方で、膵がん幹細胞の選択的排除によるヒト膵がん組織の退縮動態を確認する。
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Outline of Final Research Achievements |
The aim of this study was to establish in vitro and in vivo experimental systems that mimick human pancreatic cancer development process and to observe cancer "stem" cell behaviors in those systems. We established human pancreatic cancer organoids and inserted DCLK1-CreERT and CMV-LAL-tdTomato constructs to them. In these organoids and subsequently established xenografts, lineage tracing experiments showed that DCLK1-positive pancreatic cancer cells have a potential of cancer "stem" cells. Thus, DCLK1-positive pancreatic cancer cell might be a novel therapeutic target.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、難治がんの代表であるヒト膵がんの発育進展過程を独自の生体内外モデルで可視化する試みである。膵がんのバイオロジーと新規治療法を探索する過程で、「マウスからヒトへ」さらに「ヒトにおける実用化」を視野に入れた知見を獲得し、発展させる可能性を有する。またDCLK1陽性がん細胞は、膵がん以外のヒト消化器がんにひろく存在している。そのため、将来的により普遍性の高い「消化器がん幹細胞標的療法」という新しい治療コンセプトへの道を拓く挑戦性も備えた研究と思われた。
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Visualization of stem cell activity in pancreatic cancer expansion by direct lineage tracing with live imaging.2021
Author(s)
Maruno T, Fukuda A, Goto N, Tsuda M, Ikuta K, Hiramatsu Y, Ogawa S, Nakanishi Y, Yamaga Y, Yoshioka T, Takaori K, Uemoto S, Saur D, Chiba T, Seno H
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Journal Title
Elife
Volume: 10
Pages: e55117
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] SETDB1 Inhibits p53-Mediated Apoptosis and is Required for Formation of Pancreatic Ductal Adenocarcinomas in Mice.2020
Author(s)
Ogawa S, Fukuda A, Matsumoto Y, Hanyu Y, Sono M, Fukunaga Y, Masuda T, Araki O, Nagao M, Yoshikawa T, Goto N, Hiramatsu Y, Tsuda M, Maruno T, Nakanishi Y, Hussein MS, Tsuruyama T, Takaori K, Uemoto S, Seno H
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Journal Title
Gastroenterology
Volume: 159
Pages: 682-696
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Rb and p53 execute distinct roles in the development of pancreatic neuroendocrine tumors.2020
Author(s)
Yamauchi Y, Kodama Y, Shiokawa M, Kakiuchi N, Marui S, Kuwada T, Sogabe Y, Tomono T, Mima A, Morita T, Matsumori T, Ueda T, Tsuda M, Nishikawa Y, Kuriyama K, Sakuma Y, Ota Y, Maruno T, Uza N, Masuda A, Tatsuoka H, Yabe D, Minamiguchi S, Masui T, Inagaki N, Uemoto S, Chiba T, Seno H
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Journal Title
Cancer Res
Volume: 80
Pages: 3620-3630
DOI
Related Report
Peer Reviewed
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[Journal Article] CXCR4 in tumor epithelial cells mediates desmoplastic reaction in pancreatic ductal adenocarcinoma.2020
Author(s)
Morita T, Kodama Y, Shiokawa M, Kuriyama K, Marui S, Kuwada T, Sogabe Y, Matsumori T, Kakiuchi N, Tomono T, Mima A, Ueda T, Tsuda M, Yamauchi Y, Nishikawa Y, Sakuma Y, Ota Y, Maruno T, Uza N, Nagasawa T, Chiba T, Seno H
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Journal Title
Cancer Res
Volume: 80
Pages: 4058-4070
DOI
Related Report
Peer Reviewed
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[Journal Article] Hes1 is essential in proliferating ductal cell-mediated development of intrahepatic cholangiocarcinoma.2020
Author(s)
Matsumori T, Kodama Y, Takai A, Shiokawa M, Nishikawa Y, Matsumoto T, Takeda H, Marui S, Okada H, Hirano T, Kuwada T, Sogabe Y, Kakiuchi N, Tomono T, Mima A, Morita T, Ueda T, Tsuda M, Yamauchi Y, Kuriyama K, Sakuma Y, Ota Y, Maruno T, Uza N, Marusawa H, Kageyama R, Chiba T, Seno H
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Journal Title
Cancer Res
Volume: 80
Pages: 5305-5316
DOI
Related Report
Peer Reviewed
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[Journal Article] Epithelial EP4 plays an essential role in maintaining homeostasis in colon.2019
Author(s)
Matsumoto Y, Nakanishi Y, Yoshioka T, Yamaga Y, Masuda T, Fukunaga Y, Sono M, Yoshikawa T, Nagao M, Araki O, Ogawa S, Goto N, Hiramatsu Y, Breyer RM, Fukuda A, Seno H.
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Journal Title
Sci Rep.
Volume: 9
Pages: 15244
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lineage tracing and targeting of IL17RB+ tuft cell-like human colorectal cancer stem cells.2019
Author(s)
Goto N, Fukuda A, Yamaga Y, Yoshikawa T, Maruno T, Maekawa H, Inamoto S, Kawada K, Sakai Y, Miyoshi H, Taketo MM, Chiba T, Seno H.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 116
Pages: 12996-13005
DOI
Related Report
Peer Reviewed
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[Journal Article] Hes1 plays an essential role in Kras-driven pancreatic tumorigenesis.2019
Author(s)
Nishikawa Y, Kodama Y, Shiokawa M, Matsumori T, Marui S, Kuriyama K, Kuwada T, Sogabe Y, Kakiuchi N, Tomono T, Mima A, Morita T, Ueda T, Tsuda M, Yamauchi Y, Sakuma Y, Ota Y, Maruno T, Uza N, Uesugi M, Kageyama R, Chiba T, Seno H.
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Journal Title
Oncogene.
Volume: 38
Pages: 4283-4296
DOI
Related Report
Peer Reviewed
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[Journal Article] Bmi1 marks gastric stem cells located in the isthmus in mice.2019
Author(s)
Yoshioka T, Fukuda A, Araki O, Ogawa S, Hanyu Y, Matsumoto Y, Yamaga Y, Nakanishi Y, Kawada K, Sakai Y, Chiba T, Seno H.
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Journal Title
J Pathol.
Volume: 248
Pages: 179-190
DOI
Related Report
Peer Reviewed
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