2023 Fiscal Year Final Research Report
Analysis of the mechanism of cholangiocarcinoma progression based on intertissue crosstalk
| Project/Area Number |
21K08732
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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 | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
長井 和之 京都大学, 医学研究科, 講師 (30567871)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 胆管癌 / オルガノイド / 腫瘍内不均一性 / ドパミン / 癌幹細胞 |
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| Outline of Final Research Achievements |
Given the high affinity of cholangiocarcinoma for neural tissue, the aim of this study was to clarify the relationship between neurotransmitters and cholangiocarcinoma. Focusing on dopamine, one of the receptors, we examined its receptor expression and its effect on progression using cell line organoids and organoids derived from human cholangiocarcinoma tissue. The results revealed that among the five types of dopamine receptors, the D1 receptor is a receptor involved in stemness characterized by scaffold-independence, and that cholangiocarcinomas are not a single group but a population with different cell differentiation states and responses to dopamine signaling. We also found that Wnt7b is involved in the D1 receptor and is associated with increased stem cell fractionation.
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| Free Research Field |
肝胆膵癌
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| Academic Significance and Societal Importance of the Research Achievements |
胆管癌は本邦では年間3500例の胆管癌切除が行われる最難治癌の一つである。また、薬物治療の耐性に関与する癌幹細胞は胆管癌に関してこれまで明らかとなっていない。本研究では胆管周囲の神経に拡がる浸潤癌は成績が極めて不良であることから、胆管癌と神経組織の相互作用に着目し、神経組織から分泌されるドパミンに反応するドパミン受容体が胆管癌における幹細胞フェノタイプに関係していることを明らかにした。さらにWnt7bが幹細胞増加に重要であることを突き止めたことから、今後、この難治癌である胆管癌に対して、Wnt7bをターゲットとした治療開発により、薬物耐性改善による治療効果増強を目指すことにつなげる。
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