Mechanism elucidation of microenvironment in biliary tract cancer at initial infiltration lesion.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19328
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Hirosaki University
• Principal Investigator: Haga Toshihiro 弘前大学, 医学研究科, 助教 (80771625)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 早期胆道癌 / 初期浸潤病巣 / 時計遺伝子

Outline of Final Research Achievements

The microenvironmental characteristics of biliary tract cancer include fibrosis around the cancer cells even in early infiltration lesions, vascular invasion and perineurial infiltration. The microenvironment plays an important role in cancer malignancy.
Here, using a co-culture model of biliary cancer cell lines and human mesenchymal stem cells, we confirmed morphological changes of cancer cells and epithelial-mesenchymal transformation (EMT) that occurs in cancer cells. The clock gene, which forms circadian rhythms, also shows that the expression of the clock gene of cancer cells is elevated under the microenvironment, and it has been shown to play an important role in the formation of the cancer microenvironment. Furthermore, under the microenvironment, the interaction between cytokines (e.g. anti-tumor cytokines anti-inflammatory cytokines) and clock genes was suggested.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

胆道癌の初期浸潤病巣において時計遺伝子が関与することが示唆された。今後は間質や時計遺伝子を標的とする新たな胆道癌治療 (時計遺伝子 DEC 阻害剤薬の開発と臨床応用研究など) への基礎的研究として発展できる可能性が期待できる。さらに、本研究が胆道癌の早期発見・治療へと繋がり胆道癌全体の予後改善へ礎を成したと考えられる。