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The Role of induced lung cancer stem Like cells on invasive activity of lung adenocaricinoma

Research Project

Project/Area Number 17H04297
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory surgery
Research InstitutionKobe University

Principal Investigator

Maniwa Yoshimasa  神戸大学, 医学研究科, 教授 (50362778)

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)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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)
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
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (5 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Efficacy of perioperative chemotherapy for pulmonary high-grade neuroendocrine carcinomas: a propensity score matching analysis2019

    • Author(s)
      Ogawa Hiroyuki、Tanaka Yugo、Kitamura Yoshitaka、Shimizu Nahoko、Doi Takefumi、Hokka Daisuke、Tane Shinya、Nishio Wataru、Yoshimura Masahiro、Maniwa Yoshimasa
    • Journal Title

      Journal of Thoracic Disease

      Volume: 11 Issue: 4 Pages: 1145-1154

    • DOI

      10.21037/jtd.2019.04.56

    • NAID

      120006890789

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuroendocrine marker staining pattern categorization of small‐sized pulmonary large cell neuroendocrine carcinoma2019

    • Author(s)
      Minami Kazuhiro、Tanaka Yugo、Ogawa Hiroyuki、Jimbo Naoe、Nishio Wataru、Yoshimura Masahiro、Itoh Tomoo、Maniwa Yoshimasa
    • Journal Title

      Thoracic Cancer

      Volume: 10 Issue: 11 Pages: 2152-2160

    • DOI

      10.1111/1759-7714.13202

    • NAID

      120006764479

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Critical role of the Ror-family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells2018

    • Author(s)
      Saji Takeshi、Nishita Michiru、Ogawa Hiroyuki、Doi Takefumi、Sakai Yasuhiro、Maniwa Yoshimasa、Minami Yasuhiro
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 7 Pages: 606-613

    • DOI

      10.1111/gtc.12599

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells2017

    • Author(s)
      Ogawa Hiroyuki、Koyanagi-Aoi Michiyo、Otani Kyoko、Zen Yoh、Maniwa Yoshimasa、Aoi Takashi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12317-12317

    • DOI

      10.1038/s41598-017-12017-y

    • NAID

      120006358585

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Interleukin-6 blockade, a novel cancer stem cell targeted therapy, attenuates lung cancer tissue construction2017

    • Author(s)
      Ogawa, H., Koyanagi-Aoi, M., Aoi, T., Maniwa, Y
    • Organizer
      American Association for Cancer Research annual meeting 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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