| Project/Area Number |
17K19612
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Keio University |
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Principal Investigator |
Seino Takashi 慶應義塾大学, 医学部(信濃町), 助教 (10649940)
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| Research Collaborator |
SATO Toshiro
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 膵癌 / オルガノイド / Wnt / GATA6 / CRISPR/Cas9 |
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| Outline of Final Research Achievements |
A library consisting of 50 human pancreatic tumor organoids was successfully established. Comparison between genetic information and phenotypic traits using the library revealed that pancreatic cancers were classified into three distinct subtypes based on Wnt or Rspondin dependence, namely Wnt non-secreting, Wnt secreting and Wnt/Rspondin independent type. This categorization suggested a gradual transition of pancreatic cancers to more malignant subtype along with the acquisition of Wnt Independence.
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌をWntとRspondinという２つ細胞増殖因子に対する要求性に基づいて、３つのサブタイプ、すなわちWnt分非泌型膵癌、Wnt分泌型膵癌、Wnt/Rspo非依存型膵癌に分類可能であることを示した。Wnt非分泌型膵癌はがん細胞周囲の線維芽細胞から供給されるWntを、Wnt分泌型膵癌は自己産生しているWntを化合物を用いて阻害することで増殖抑制が可能であることを示した。したがって、膵癌の治療標的の一つとしてWntシグナルが考えられ、臨床応用の可能性があることを明らかにした。
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