2021 Fiscal Year Final Research Report
Plasticity of cancer-initiating and cancer cells in intrahepatic cholangiocarcinoma and regulation of the cancer stromal microenvironment
| Project/Area Number |
19K09113
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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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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高野 重紹 千葉大学, 医学部附属病院, 講師 (20436380)
久保木 知 千葉大学, 大学院医学研究院, 講師 (50571410)
中台 英里 千葉大学, 医学部附属病院, 助教 (60831500)
三島 敬 千葉大学, 医学部附属病院, 助教 (70802560)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 肝内胆管癌 / 癌源細胞 / Notchシグナル / Wntシグナル / 上皮間葉転換 / stemness / 癌間質微小環境 / p-FAK |
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| Outline of Final Research Achievements |
Notch2 and LGR5 were expressed in 56% and 72% of cases with intrahepatic cholangiocarcinoma, respectively. In vivo and in vitro studies suggested that Notch2 is involved in the differentiation of intrahepatic cholangiocarcinoma cells into more mature cholangiocyte-like cells, resulting in reduced aggressiveness, while LGR5 may be involved in the stemness of intrahepatic cholangiocarcinoma cells, and increase their aggressiveness. In addition, Wnt signaling is also involved in the acquisition of EMT and stemness and was suggested to play an important role in the induction and maintenance of cancer-initiating cells. Furthermore, p-FAK was expressed in 60% of intrahepatic cholangiocarcinoma cases, and the survival of patients with positive p-FAK expression was significantly worse than that of patients with negative p-FAK expression. It was also found that p-FAK may be involved in the CAF activation.
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| Free Research Field |
医歯薬系 外科系臨床医学・消化器外科学
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| Academic Significance and Societal Importance of the Research Achievements |
肝内胆管癌は，生物学的多様性に富む腫瘍であり、その予後も症例によって大きく異なる。本研究ではそのような疾患に対し，その異なる悪性度を引き起こすメカニズムを癌細胞の分化動態に注目し、Notch シグナルとWntシグナルがその過程に重要であることを明らかにした。また、癌間質微小環境のCAFの活性化が本疾患の悪性度を高め、そこにはp-FAKの発現が重要である可能性を見出した。これらは本疾患に対する新たな治療法開発の基礎となるものと考えられた。
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