2022 Fiscal Year Final Research Report

Exploring a new regulation system of pancreatic cancer microenvironment using KPC confetti mice

Research Project

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Project/Area Number	20K09057
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Kyushu University
Principal Investigator	YASUI Takaharu 九州大学, 医学研究院, 共同研究員 (60611283)
Co-Investigator(Kenkyū-buntansha)	木庭遼九州大学, 医学研究院, 共同研究員 (10866776) 藤田逸人九州大学, 医学研究院, 共同研究員 (40611281) 坂井寛九州大学, 医学研究院, 共同研究員 (80611665) 冨永洋平宮崎大学, 医学部, 講師 (90304823) 大内田研宙九州大学, 医学研究院, 准教授 (20452708)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	膵癌自然発生マウス / 4色発現マウス / 膵癌 / 微小環境 / 微小転移
Outline of Final Research Achievements	In pancreatic cancer, liver metastasis is cause of poor prognosis. Liver metastases of pancreatic cancer are highly malignant and there is no effective treatment for them. We will clarify the mechanism of metastasis at very early stage using KPC Confetti mice, in which pancreatic cancer cells randomly fluoresce. We identified multicolor cancer cells in primary tumors, but not in metastases. Therefore, we focused on activated hepatic stellate cells, which are involved in the formation of hepatic metastasis, to elucidate the metastatic mechanism. We screened for candidate drugs that induce pancreatic stellate cells inactivation, which we had identified in a previous study. Several drugs showed decreased expression of αSMA, the accumulation of lipid droplets in the hepatic stellate cells, and inhibited the activation of hepatic stellate cells. It was suggested that inactivation of hepatic stellate cells inhibits hepatic metastasis formation.
Free Research Field	医歯薬学
Academic Significance and Societal Importance of the Research Achievements	微小転移モデルには細胞株の同所移植モデルが用いられてきたが、ヒト膵癌と相同性が低い問題があった。KPC Confettiマウスを用いることでヒト膵癌と病理学的類似性が高い腫瘍の極早期の微小転移を単細胞レベルで解析でき、微小転移に関わる細胞集団が同定できれば、癌細胞集団の特徴的や間質・免疫細胞の役割など今まで解明されていない分野への貢献も期待される。本研究により膵癌の微小転移のメカニズムが解明され新たな治療法の開発に至れば、難治性である膵癌の予後改善のみならず、他癌腫の転移メカニズム解析にも応用でき、学術的・社会的にも広範な波及効果が期待される為、癌研究分野において非常に意義が高いと考えられる。