2022 Fiscal Year Final Research Report

Mechanisms determining the wide spectrum of hepatocytic tumors

Research Project

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Project/Area Number	19H03448
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 49030:Experimental pathology-related
Research Institution	Asahikawa Medical College
Principal Investigator	Nishikawa Yuji 旭川医科大学, その他, 学長 (90208166)
Co-Investigator(Kenkyū-buntansha)	後藤正憲旭川医科大学, 医学部, 助教 (00432203) 藤井裕美子旭川医科大学, 医学部, 助教 (30722334) 田中宏樹旭川医科大学, 医学部, 助教 (70596155) 人見淳一旭川医科大学, 医学部, 助教 (40568664)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	肝腫瘍 / 肝細胞癌 / 胆管細胞癌 / 混合型肝癌 / 分化転換 / 脱分化
Outline of Final Research Achievements	Primary liver cancers include various types of histological types: hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, et al. Hepatocytes retain phenotypic plasticity even after being fully matured and could undergo ductular transdifferentiation, dedifferentiation, and epithelial-mesenchymal transition in response to the changes in microenvironment or gene expression. In this study, using a transposon-mediated oncogene integration system in vivo and in vitro with combination with p53 knockout in mouse hepatocytes, we demonstrated that hepatocytes could demonstrate a wide spectrum of tumor phenotypes and revealed several intracellular signaling pathways involved in the phenotypic plasticity of hepatocytic tumors.
Free Research Field	Pathology
Academic Significance and Societal Importance of the Research Achievements	原発性肝癌は現在も予後の悪い悪性腫瘍であり、その病態解明が強く望まれている。原発性肝癌の主要なタイプは肝細胞癌と胆管細胞癌であり、それぞれ肝細胞およおび胆管上皮細胞由来と考えられてきたが、肝細胞の表現型の可塑性が明らかになり、胆管細胞癌やその他の肝癌の細胞起源について活発な議論が行われている。我々は本研究で肝細胞由来腫瘍が肝細胞癌だけでなく、幅広いスペクトラムの組織型を示しうることを証明し、その分子メカニズムの一端を明らかにした。我々が得た知見は、原発性肝癌の病態の理解を深めるとともに、新たな治療戦略の基礎となりうると考えられる。