| Project/Area Number |
21K08321
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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 53050:Dermatology-related
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| Research Institution | University of Fukui |
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Principal Investigator |
Oyama Noritaka 福井大学, 学術研究院医学系部門, 准教授 (30332927)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 細胞外基質 / 皮膚癌微小環境 / 黒色腫 / 有棘細胞癌 / ECM1 / 腫瘍浸潤 / 腫瘍転移 / マウスモデル / 間葉転換 / 癌微小環境 / 皮膚がん |
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| Outline of Research at the Start |
本研究では、細胞外基質の１つであるECM1が皮膚癌の周辺微小環境を整え、癌の多彩な間葉転換と免疫回避能の制御に及ぼす役割を解析する．さらに細胞外基質の機能変化を発端とする新たな癌寛容機構の解明を目指す．ECM1欠損マウスの皮膚に種々の担癌状態を誘導し、癌の生着能と進展様式を評価する．癌微小環境の細胞外基質と免疫担当細胞の変化を網羅的に解析し、特定の細胞外基質に依存する癌の免疫応答と進展の機序を理解する．これらをヒト皮膚癌と比較し、ECM1が皮膚の老化発癌を制御する癌間質マスター分子である可能性を追求し、周辺間質分子の標的治療を視野にいれた臨床応用の基盤の構築を目指す．
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| Outline of Final Research Achievements |
ECM1-deficient mice were transplanted with skin-derived cancer cell lines (spinous cell carcinoma and melanoma) to analyze the mechanisms of their local maintenance and progression. Conventional methods were used to generate ECM1 gene-deficient mice, but all of them died during the embryonic period. This result suggests that ECM1 is not only a disease susceptibility gene but also a developmentally important molecule. We next created an organ-specific ECM1-deficient state by a conditioned KO method, and further analyzed cultured dermal fibroblasts treated by the siRNA method targeting ECM1 gene alone.
The KO human model for ECM1 gene, mucocutaneous hyalinosis, is a genetic disease without fetal lethality or prognostic value for life. The present results indicate a differential, unidentified ECM1 function between human and mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果が癌間質分子を標的とする創薬に結び付いた際には、癌自体を標的とする既存の抗癌剤との併用も可能な作用機序である点からも、相乗効果や耐性の獲得を一層回避できる治療戦略を構築できる可能性が高く、学術的にも社会的にも貢献度の高い研究テーマであると考えている．
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