2020 Fiscal Year Final Research Report

New humoral factor facilitates hepato-biliary and pancreatic cancer progression and development of innovative thrapy

Research Project

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Project/Area Number	18H02877
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Gunma University
Principal Investigator	Shirabe Ken 群馬大学, 大学院医学系研究科, 教授 (70264025)
Co-Investigator(Kenkyū-buntansha)	播本憲史群馬大学, 医学部附属病院, 講師 (00419582) 石井範洋群馬大学, 医学部附属病院, 助教 (00711508) 久保憲生群馬大学, 医学部附属病院, 助教 (10464744) 五十嵐隆通群馬大学, 医学部附属病院, 助教 (20648472) 市川聡北海道大学, 薬学研究院, 教授 (60333621) 横堀武彦群馬大学, 未来先端研究機構, 准教授 (60420098) 新木健一郎群馬大学, 大学院医学系研究科, 助教 (60431706) 渡辺亮群馬大学, 医学部附属病院, 助教 (60738847) 塚越真梨子群馬大学, 大学院医学系研究科, 助教 (60781317)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	肝胆膵がん / 癌関連線維芽細胞 / M2BPGi
Outline of Final Research Achievements	M2BPGi and galectin-3 proteins co-localised in HCC cells, while M2BP mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC. M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway. Therefore, galectin 3 inhibitor would be quite effective in M2BPGi. We have already developed the prototype galectin 3 inhibitor and we are now on the way of new galectin 3 inhibitor production, which has extremely high affinity to galectin 3.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	難治癌の代表とされる肝胆膵がんの増殖進展において癌関連線維芽細胞が重要な役割を担っていることが明らかになった。さらに癌関連線維芽細胞と癌細胞の連関においてM2BPGiという肝線維化の新規血清マーカーが癌関連線維芽細胞や肝硬変の星細胞で産生され、癌細胞の増殖・進展を促進する新たな分子機序が明らかになった。その連関を遮断するgalectin 3阻害剤の有用性が示唆された。