| Project/Area Number |
19K21278
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| Project/Area Number (Other) |
18H06169 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0901:Oncology and related fields
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| Research Institution | Juntendo University |
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Principal Investigator |
Takumi Itoh 順天堂大学, 医学(系)研究科(研究院), 博士研究員 (80811835)
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| Project Period (FY) |
2018-08-24 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Th17 / IL-26 / 炎症性サイトカイン / 悪性黒色腫 / 癌微小環境 / 腫瘍免疫 / 癌転移 / 上皮間葉転換 |
|---|
| Outline of Research at the Start |
本研究ではIL-26分子標的治療の有効性評価を行うため、高転移性悪性黒色腫における癌微小環境中で産生されるIL-26が腫瘍の高転移能獲得のどのステージに関与しているのか明らかにする。これにより、最も予後の悪い遠隔転移性の悪性黒色腫を根絶する新たな分子標的療法を提供するとともに様々な転移性癌の治療応用と微小環境におけるTh17細胞の役割の解明にも繋がることが期待される。
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| Outline of Final Research Achievements |
We recently show that the Th17 cytokine IL-26 promotes angiogenesis and activates fibroblasts in inflammatory conditions, while its role in tumor microenvironment still remains to be elucidated.
Since IL-26 is absent in rodents, human IL-26 transgenic (hIL-26Tg) mice were used in our study. After subcutaneous transplantation of murine melanoma B16F10 cells into hIL-26Tg mice, sarcoma-like transformation, upregulation of Snail1were observed. To investigate the metastatic potential of IL-26-educated B16F10, B16F10 cells resected from the subcutaneous tissue of hIL-26Tg mice were intravenously injected into C57BL/6 wild-type mice. Lung metastasis was prominently observed following injection of IL-26-educated cells as compared with control mice-derived cells. Our results suggest that IL-26 promotes melanoma metastasis through Snail1-mediated epithelial-mesenchymal transition, and blockade of IL-26 appears to be a promising novel therapeutic strategy for the control of tumor metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではヒトIL-26トランスジェニックマウスを用いた担癌モデルを作製してIL-26の機能の詳細な解明を行っており、これまで明らかにならなかった癌微小環境でのIL-26の機能を明らかにし、IL-26が癌の転移能を亢進させる新しいメカニズムを明らかにした。これにより、根治が難しい癌転移における新しい治療の開発や免疫治療法の開発に繋がることが期待される。
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