Role of omega-3 fatty acid metabolism in cancer stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19353
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Hiroshima University
• Principal Investigator: Naka Kazuhito 広島大学, 原爆放射線医科学研究所, 准教授 (70372688)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: オメガ3脂肪酸 / DHA代謝 / CML幹細胞 / Gタンパク質共役受容体 / mTORC1経路

Outline of Final Research Achievements

In this study, we investigated a role of omega-3 fatty acid-mediated signaling pathway for the maintenance of self-renewal capacity of chronic myelogenous leukemia (CML) stem cells by using a CML mouse model in vivo. We found that murine CML stem cells highly expressed G-protein coupled receptor Gpr82 gene than normal hematopoietic stem cells by RNA-sequencing. Recipient mice transplanted with Gpr82-deficient CML stem cells shortened survival period than those transplanted with control (wild type) CML stem cells. Interestingly, absolute number of Gpr82-deficient CML stem cells in spleen decreased than control CML stem cells after 12 days of bone marrow transplantation. These results suggested that Gpr82 plays an important role for the maintenance of self-renewal capacity of CML stem cells in vivo.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

慢性骨髄性白血病 (CML)患者の生命予後はチロシンキナーゼ阻害剤 (TKI)の開発によって飛躍的に向上したが，再発が問題となっており，CML幹細胞はこのようなCMLの再発の原因となることが知られている．本研究では, CMLのマウスモデルを用いて，生体内でのCML幹細胞の維持におけるオメガ3脂肪酸代謝の意義を解析した．その結果， ドコサヘキサエン酸(DHA)は下流のGタンパク質共役受容体を介してmTORC1経路の不活化によりCML幹細胞の未分化性維持に関わる可能性が明らかとなった．従って，Gタンパク質共役受容体はCML幹細胞を根絶してCMLの再発を克服するための治療標的となることが示唆された．