The Role of induced lung cancer stem Like cells on invasive activity of lung adenocaricinoma
| Project/Area Number |
17H04297
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory surgery
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
青井 貴之 神戸大学, 科学技術イノベーション研究科, 教授 (00546997)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 肺癌 / 発生・分化 / トランスレーショナルリサーチ / 癌幹細胞 / バイオテクノロジー / 肺腺癌 / 癌微小環境 / 癌宿主相互作用 / iPS細胞 |
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| Outline of Final Research Achievements |
In this study, we successfully generated induced lung cancer stem like cells (iLCSC) by introducing OCT3/4, SOX2, KLF4 into A549 cells. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named them “lung cancer organoids”. We found that interleukin-6 (IL-6), which was strongly expressed in iLCSC, facilitates the formation of lung cancer organoids via the conversion of mesenchymal stem cells into alpha-smooth muscle actin (αSMA)-positive cells. Interestingly, the combination of anti-IL-6 antibody and cisplatin could destroy the lung cancer organoids, while cisplatin alone could not. These results suggest that IL-6 could be a novel therapeutic target in lung cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で用いた肺癌オルガノイドの系により、肺癌幹細胞とその周囲間質細胞をターゲットにした薬剤スクリーニングが可能となる。従来の抗癌剤の感受性評価の方法として、in vivoで免疫不全マウスに対するゼノグラフトを用いた手法が頻用されている。しかし、この手法はわずか数種類の薬剤やその組み合わせによる効果を検討するにも、膨大な時間と労力を有する。本アッセイを用いることにより、より効率的な手法による多数の薬剤のスクリーニングが可能になると考えられる。我々は、本アッセイを用いてIL-6の遮断が肺癌幹細胞をターゲットにした治療になりうることを明らかにしているが、他の新規治療薬発見にもつながると考えられる。
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Report
(4 results)
Research Products
(5 results)
