Novel Exosome Biology with sPLA2
| Project/Area Number |
20K21550
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | Tokai University |
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Principal Investigator |
Kotani Ai 東海大学, 医学部, 教授 (00517477)
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| 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)
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 細胞外小胞 / リンパ腫 / s PLA2 / エクソソーム / sPLA2 |
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| Outline of Research at the Start |
エクソソームが標的細胞に取り込まれないと機能しないという古典的概念を覆す現象「標的細胞に取り込まれることなく、体液中に存在する酵素、分泌型リン脂質加水分解酵素(sPLA2)と反応し、強力な生理活性物質をエクソソーム上で産生することによって生物学的効果を発揮しうる」の細胞での効果とその分子機序、癌における生物学的意義を解明し、新しいエクソソームバイオロジーを構築する。
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| 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.
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| 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
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Proteomic and phospholipidomic characterization of extracellular vesicles inducing tumor microenvironment in Epstein-Barr virus-associated lymphomas.2021
Author(s)
Ito M, Kudo K, Higuchi H, Otsuka H, Tanaka M, Fukunishi N, Araki T, Takamatsu M, Ino Y, Kimura Y, Kotani A.
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Journal Title
FASEB J.
Volume: 35
Issue: 4
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Rap1 is essential for B-cell locomotion, germinal center formation and normal B-1a cell population.2021
Author(s)
Ishihara S, Sato T, Sugioka R, Miwa R, Saito H, Sato R, Fukuyama H, Nakajima A, Sawai S, Kotani A, Katagiri K.
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Journal Title
Front Immunol.
Volume: 12
Pages: 624419-624419
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Overexpression of miR-669m inhibits erythroblast differentiation2020
Author(s)
Kotaki R., et.al. Kawashima M, Yamaguchi A, Suzuki N, Koyama-Nasu R, Ogiya D, Okuyama K, Yamamoto Y, Takamatsu M, Kurosaki N, Ando K, Murata A, Ohtsuka M, Nakagawa S, Katagiri K, Kotani A.
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Journal Title
Sci Rep.
Volume: 10
Issue: 1
Pages: 13554-13554
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] PD-L1/L2 protein levels rapidly increase on monocytes via trogocytosis from tumor cells in classical Hodgkin lymphoma2020
Author(s)
Kawashima M, Carreras J, Higuchi H, Kotaki R, Hoshina T, Okuyama K, Suzuki N, Kakizaki M, Miyatake Y, Ando K, Nakayama M, Umezu S, Horie R, Higuchi Y, Katagiri K, Goyama S, Kitamura T, Chamoto K, Yano S,Nakamura N, and A Kotani
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Journal Title
Leukemia
Volume: -
Issue: 9
Pages: 2405-2417
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Interferon-γ induced PD-L1 expression and soluble PD-L1 production in gastric cancer.2020
Author(s)
Imai Y, Chiba T, Kondo T, Kanzaki H, Kanayama K, Ao J, Kojima R, Kusakabe Y, Nakamura M, Saito T, Nakagawa R, Suzuki E, Nakamoto S, Muroyama R, Tawada A, Matsumura T, Nakagawa T, Kato J, Kotani A, Matsubara H, Kato N.
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Journal Title
Oncol Lett
Volume: 20
Issue: 3
Pages: 2161-2168
DOI
Related Report
Peer Reviewed
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[Journal Article] Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines.2020
Author(s)
2)Kotaki R, Kawashima M, Yamamoto Y, Higuchi H, Nagashima E, Kurosaki N, Takamatsu M, Kikuti YY, Imadome KI, Nakamura N, *Kotani A.
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Journal Title
Sci Rep.
Volume: 10(1):
Issue: 1
Pages: 4355-4355
DOI
Related Report
Peer Reviewed / Open Access
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