Elucidation of a novel cell signaling mechanism by lipid mediators and bile acids in biliary diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15610
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Niigata University
• Principal Investigator: WAKAI TOSHIFUMI 新潟大学, 医歯学系, 教授 (50372470)
• Co-Investigator(Kenkyū-buntansha): 永橋 昌幸 新潟大学, 医歯学総合病院, 研究准教授 (30743918) ; 小林 隆 新潟大学, 医歯学総合病院, 講師 (40464010) ; 坂田 純 新潟大学, 医歯学系, 講師 (70447605)
• Research Collaborator: Kameyama Hitoshi ; Katada Tomohiro ; Hirose Yuki ; Ando Takuya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 脂質メディエーター / スフィンゴシン-1-リン酸 / 胆汁酸 / 胆道疾患 / 細胞情報伝達機構 / 胆道癌 / リンパ行性進展転移

Outline of Final Research Achievements

It has been revealed that bile acids work not only as detergent in the biliary tract and intestine, but also as signaling molecules that cause a variety of biological effects. We have previously reported that bile acids act directly on specific receptors of the lipid mediator, sphingosine-1-phosphate (S1P), to activate intracellular signal transduction. In this study, we investigated bile acids and S1P signaling in biliary diseases (cholecystitis, gallbladder cancer, cholangiocarcinoma, etc.). In this study, we measured S1P levels in bile and tissue in patients with each biliary disease, and revealed that S1P levels were significantly elevated in biliary tract cancer tissue compared with normal tissue. Furthermore, we revealed that S1P plays an important role in the lymphatic metastasis of biliary tract cancer.

Free Research Field

消化器外科学関連

Academic Significance and Societal Importance of the Research Achievements

本研究は、胆道疾患において胆汁及び組織中のS1P濃度を質量分析装置で測定した初めての研究であり、学術的に意義がある。また、ヒトの胆道癌組織を用いた解析により、生体内の胆道癌組織においてもこれまでの基礎実験と同様、S1Pが癌のリンパ行性転移に寄与していることを明らかにしたことは臨床的に意義がある。今後、胆道癌のリンパ行性転移におけるS1Pの役割を明らかにすることで、胆道癌のリンパ行性進展転移を制御する新たな治療法開発へつながる可能性が期待される。