| Project/Area Number |
19K18758
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Gunma University |
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Principal Investigator |
MITO IKKO 群馬大学, 医学部附属病院, 助教 (10836711)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | エクソソーム / 癌微少環境 / 頭頸部癌 / CAFs / 炎症性サイトカイン / がん微少環境 / RNA-seq / 次世代シーケンス / 癌微小環境 / 線維芽細胞 / HPV / PCR / フローサイトメトリー |
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| Outline of Research at the Start |
癌微小環境を構成する細胞として癌細胞とその周囲を取り巻く間質細胞がある。このうち、T細胞、癌関連線維芽細胞（cancer-associated fibroblasts: CAFs）を中心に、癌微小環境形成における癌細胞とこれらの間質細胞間のエクソソームを介した相互作用を明らかにすることで、新しいバイオマーカーや治療ターゲットの同定に結び付ける。
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| Outline of Final Research Achievements |
Exosomes were extracted from the squamous cell carcinoma cell line of the head and neck and acted on normal fibroblasts to analyze the changes. In addition, the supernatant of fibroblasts treated with exosomes, normal T cells and CD14-positive cells were co-cultured, and functional analysis was performed by flow cytometry.
Proliferation was promoted in fibroblasts treated with cancer cell-derived exosomes. Genetic analysis showed increased gene expression of IL6, CXCL8, FAP, IL1B, CD274, ACTA2, and TGFβ by PCR, and RNA-seq analysis targeted inflammatory cytokines such as IL-6 / CXCL8 / IL-17. An increase in the canonical pathway was observed. In addition, co-culture with exosomes suppressed the proliferation of normal T cells and CD14-positive cells. It is possible that head and neck cancer-derived exosomes act on normal fibroblasts, promote cell proliferation, induce CAFs, and contribute to the construction of the cancer microenvironment.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究で、頭頸部癌由来エクソソームが正常な線維芽細胞に作用し、細胞増殖を促進し、CAFsを誘導し、癌の微小環境の構築に関与している可能性が考えられた。今後の展開としては、頭頸部癌患者の採血等の検査からエクソソームを抽出・検出することで早期発見や診断に繋げる事や、エクソソーム自体の阻害や産生の抑制を行うことで新たな抗癌作用の薬剤の開発などが期待できる。
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