Novel Exosome Biology with sPLA2

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21550
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Tokai University
• Principal Investigator: Kotani Ai 東海大学, 医学部, 教授 (00517477)
• Co-Investigator(Kenkyū-buntansha): 村上 誠 東京大学, 大学院医学系研究科(医学部), 教授 (60276607)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 細胞外小胞

Outline of Final Research Achievements

In this study, we demonstrated that sPLA2 secreted by tumor-associated macrophages (TAMs) in malignant lymphoma tissue 2 secreted by tumor-associated macrophages (TAMs) in malignant lymphoma tissue degrades phospholipids in tumor cell-derived EVs. Furthermore, we found that this degradation dramatically improves the functions of EVs, such as "ease of cellular uptake" and "immunosuppressive effect," and induces various biological phenomena. In this case, they discovered that lysophospholipid, a degradation product of EV phospholipids, is involved in signaling to cells through a novel operating mechanism that has never been observed in EV biology before. The research group has also discovered a novel mechanism of EV signaling in human lymphomas. Using a mouse model of human lymphoma development, the research group demonstrated that sPLA2-mediated EV degradation is essential for tumorigenesis.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではリンパ腫由来ＥＶのみならず他のがん細胞由来ＥＶもｓＰＬＡ２により分解されることを証明し、ｓＰＬＡ２－ＥＶ軸は腫瘍形成において共通の現象であることを明らかにしました。今後はこのｓＰＬＡ２－ＥＶ軸が新たな「免疫チェックポイント」として、がん治療のための新しい薬物標的となることが期待されます。また本研究で証明されたｓＰＬＡ２によるＥＶ機能の増強効果から、過去に幸谷グループで報告した「組織保護・抗炎症作用を持つＥＶ」などのさまざまな種類のＥＶが持つ固有の能力をｓＰＬＡ２が増強するのではないかという仮説の検証も現在行っており、今後は治療的応用への発展も期待されます