2020 Fiscal Year Final Research Report
The role of disseminated tumor cells-derived exosomes in lung cancer metastasis and the molecular mechanism of lung cancer dormancy
| Project/Area Number |
18K08799
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
池田 徳彦 東京医科大学, 医学部, 主任教授 (70246205)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 転移 / エクソソーム |
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| Outline of Final Research Achievements |
This study investigated the role of disseminated tumor cells and their exosomes in terms of metastasis and invasion process. Cell proliferation and tumor dormancy-related and epithelial-mesenchymal transition marker expressions were assessed. A non-small cell lung cancer cell line of H1299 cells showed the positive relationship between the expression of mesenchymal markers and the decreased expression of tumor dormancy markers, including miR23b/miR190a. Patient-derived serum samples were collected. We classified patients into several groups according to pathological intravascular invasion status, the presence of recurrence, and time of recurrences (early recurrence and late recurrence) and extracted exosomes from their serum samples. A small RNA sequence was performed, and several novel miRNAs associated with late recurrence and tumor cell dormancy were identified. Those miRNAs, including miR23b/190a, were relevant to the presence of intravascular invasion.
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| Free Research Field |
呼吸器外科
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| Academic Significance and Societal Importance of the Research Achievements |
本研究におけるin vitro解析において、既知の腫瘍細胞休眠関連遺伝子と上皮間葉系転換マーカー発現との間に相関性を認めた。また腫瘍休眠関連指数高値の細胞株由来のエクソソームと受容細胞との共培養によって、受容細胞の形質転換が生じ、間葉系及び腫瘍細胞休眠関連マーカー発現値が増加することがわかり、播種性腫瘍細胞由来エクソソームの役割について一部証明することができた。また患者血清由来エクソソームを用いた解析では晩期再発例の術前血清由来エクソソーム中に特異的な遺伝子を同定した。本研究で初めて早期肺癌患者血清由来エクソソーム中に腫瘍細胞休眠関連遺伝子が存在することを証明できた。
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