A novel therapeutic strategy for malignant tumors by regulating the influx of extracellular Arachidonic acid

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20838
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: The Institute for AIM Medicine (2023); Tokai University (2022)
• Principal Investigator: Kudo Kai 一般社団法人AIM医学研究所, 研究部門, リサーチフェロー (60967165)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 脂質代謝 / 過酸化脂質 / Ferroptosis / 悪性リンパ腫 / がん

Outline of Final Research Achievements

Tumor cells are known to regulate intracellular and extracellular lipid composition to create a microenvironment favorable for their own survival, but the details of the molecular mechanisms and biological significance of this regulation are unknown. In this study, we found that tumor cells acquire resistance to ferroptosis and promote tumor growth by decreasing intracellular AA levels by regulating the expression of FATP2, a transporter of arachidonic acid (AA), a proinflammatory lipid. Public database analysis of TCGA and xenograft models revealed that the above-mentioned regulatory mechanism of extracellular lipid influx also plays an important role in tumor growth in poor prognosis cancers such as glioblastoma and melanoma.

Free Research Field

脂質生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかとなった悪性腫瘍の持つ脂質制御機構の一つであるFATP2の発現量は、リンパ腫のみならず多くのがんにおける予後予測マーカーとなり得る可能性が示された。今後は悪性腫瘍や過活動状態の免疫細胞を標的とした本分子の発現誘導法やリポソームを用いたアラキドン酸輸送法の検討を通じて、より副作用の少ない新規治療戦略の開発へと繋がることが期待される。