2021 Fiscal Year Final Research Report
Macrophage-mediated transfer of cancer-derived components to stromal cells creates a pro-tumor microenvironment
Project/Area Number |
19H03495
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 50010:Tumor biology-related
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Research Institution | Akita University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
栗山 正 秋田大学, 医学系研究科, 准教授 (30398226)
伊藤 剛 秋田大学, 医学系研究科, 助教 (60607563)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | がん間質 / マクロファージ / 中皮細胞 / 細胞外小胞 / 情報伝達 |
Outline of Final Research Achievements |
Cancer cells create heterogeneous pro-tumor stromal cells in microenvironments. We previously identified that macrophages (MΦ) uptake cancer cell-derived extracellular vesicles (CEV), and transfer some contents to other stromal cells via release of membrane blebs. In this study, we identified that MΦs incorporated CEVs from GM3 synthase high cancer cells induced immune checkpoint molecules in T cells, thereby caused immunosuppression. In addition, these MΦs also transformed the peritoneal mesothelial cells, which accelerated peritoneal metastasis. These findings suggest a novel crosstalk of MΦ and other stromal cells via transfer of CEV contents, and GM3 synthase may become a useful targeting molecule.
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Free Research Field |
腫瘍生物
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Academic Significance and Societal Importance of the Research Achievements |
癌をサポートする様々な間質細胞が広範囲に作られる事は、腫瘍の進行を大きく助けている。癌細胞からマクロファージへ、さらに第三の間質細胞へ伝搬する分子特性を明らかにする事で、腫瘍内間質細胞の連鎖的な活性化の様式が見えてくる。今回ガングリオシド代謝酵素などが、その機構に関わる事が分かり、その遮断により腫瘍促進性の間質の拡大を抑制する新規分子治療に繋げてゆきたい。
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