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Functional analysis of cancer stroma in the development and invasion of lung cancer using three-dimensional cell culture

Research Project

Project/Area Number 17K15638
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionThe University of Tokyo

Principal Investigator

Morita Shigeki  東京大学, 医学部附属病院, 登録研究員 (30707021)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords肺癌 / 間質 / 3次元培養 / 浸潤 / 癌関連線維芽細胞 / 病理学 / 癌間質 / 三次元培養
Outline of Final Research Achievements

In this study, we established an invasion model of lung cancer and fibroblast cell line using three-dimensional culture. Additionally, we prepared formalin-fixed paraffin-embedded specimens of the invasion model and immunohistochemically confirmed that cancer-associated fibroblast (CAF) -related factors such as α-SMA and CD10 were upregulated in fibroblasts. We also examined the changes of microRNA expression in fibroblasts by in situ hybridization.
In the investigation of surgical specimens, high expression of CAF-related factors such as calumenin and miR-21 in CAFs were a poor prognostic factor. In addition, functional analysis using cell lines also suggested that they interact and promote invasion of lung adenocarcinoma.

Academic Significance and Societal Importance of the Research Achievements

近年肺癌の研究では間質の変化が注目されてきているが、本研究では3次元培養(層状培養)の新規手法を確立し、癌周囲の線維芽細胞に見られる因子(α-SMA、calumenin等)やmicroRNAの局在、発現の変化を捉えることで、肺腺癌の発生・浸潤過程における間質の役割について新たな知見を加え,補強することになったと考えられる。また、これらの知見は新たな診断マーカーや治療ターゲットにつながる可能性がある。

Report

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

    (13 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (8 results)

  • [Journal Article] Clinicopathological significance of microRNA-21 in extracellular vesicles of pleural lavage fluid of lung adenocarcinoma and its functions inducing the mesothelial to mesenchymal transition2020

    • Author(s)
      Watabe Shiori、Kikuchi Yoshinao、Morita Shigeki、Komura Daisuke、Numakura Satoe、Kumagai‐Togashi Arisa、Watanabe Masato、Matsutani Noriyuki、Kawamura Masafumi、Yasuda Masanori、Uozaki Hiroshi
    • Journal Title

      Cancer Medicine

      Volume: 9 Issue: 8 Pages: 2879

    • DOI

      10.1002/cam4.2928

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ALK陽性肺腺癌の組織学的マーカーとしてのクララ細胞様細胞の高頻度な出現(Frequent appearance of club cell(Clara cell)-like cells as a histological marker for ALK-positive lung adenocarcinoma)2019

    • Author(s)
      Miyata‐Morita Kana、Morita Shigeki、Matsutani Noriyuki、Kondo Fukuo、Soejima Yurie、Sawabe Motoji
    • Journal Title

      Pathology International

      Volume: 69 Issue: 12 Pages: 688

    • DOI

      10.1111/pin.12864

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spread through air spaces is an independent predictor of recurrence in stage III (N2) lung adenocarcinoma.2019

    • Author(s)
      Terada Y, Takahashi T, Morita S, Kashiwabara K, Nagayama K, Nitadori JI, Anraku M, Sato M, Shinozaki-Ushiku A, Nakajima J.
    • Journal Title

      Interact Cardiovasc Thorac Surg.

      Volume: 印刷中 Issue: 3 Pages: 442-448

    • DOI

      10.1093/icvts/ivz116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-21 in cancer-associated fibroblasts supports lung adenocarcinoma progression.2018

    • Author(s)
      Kunita A, Morita S, Irisa TU, Goto A, Niki T, Takai D, Nakajima J, Fukayama M
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 1276-1288

    • DOI

      10.1038/s41598-018-27128-3

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Does lung cancer surgery cause circulating tumor cells?-A multicenter, prospective study2017

    • Author(s)
      Matsutani N, Sawabata N, Yamaguchi M, Woo T, Kudo Y, Kawase A, Shiono S, Iinuma H, Morita S, Kawamura M.
    • Journal Title

      J Thorac Dis.

      Volume: 9 Issue: 8 Pages: 2419

    • DOI

      10.21037/jtd.2017.07.33

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 肺腫瘍の術中迅速組織診における捺印細胞診併用の有用性についての検討2019

    • Author(s)
      宮田佳奈, 森田茂樹, 向山淳児, 赤嶺亮, 石井美樹子, 斉藤光次, 笹島ゆう子, 近藤福雄
    • Organizer
      第60回 日本臨床細胞学会総会(春期大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肺癌における胸腔洗浄液中の細胞外分泌小胞内miR-21の臨床病理学的意義と機能2019

    • Author(s)
      渡部朱織, 菊地良直, 森田茂樹, 河村大輔, 沼倉里枝, 渡邉雅人, 松谷哲行, 川村雅文, 安田政実, 宇於崎宏
    • Organizer
      第78回 日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肺癌における肥満細胞浸潤に関する臨床病理学的検討2019

    • Author(s)
      山内直子, 国田朱子, 森田茂樹, 日向宗利, 牛久綾, 深山正久
    • Organizer
      第108回 日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肺腺癌組織および術前胸腔洗浄液中細胞外分泌小胞に含まれるmiR-21の発現は胸膜浸潤と相関する2018

    • Author(s)
      渡部朱織,菊地良直,森田茂樹,富樫有紗,渡邊雅人,松谷哲行,川村雅文,安田政実,宇於崎宏
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 後腹膜原発腺癌の一例2018

    • Author(s)
      占部秀典、安藤純世、森田茂樹、森正也
    • Organizer
      第79回 日本病理学会関東支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腸管子宮内膜症由来と考えられた腺癌の一例2018

    • Author(s)
      占部秀典、安藤純世、森田茂樹、森正也
    • Organizer
      第80回 日本病理学会関東支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺癌胸腔洗浄液中のエクソソーム内miR-21発現量は細胞診判定と胸膜浸潤を反映する2018

    • Author(s)
      渡部朱織,菊地良直,森田茂樹,富樫有紗,渡邊雅人,松谷哲行,川村雅文,安田政実,宇於崎宏
    • Organizer
      第57回日本臨床細胞学会秋期大会
    • Related Report
      2018 Research-status Report
  • [Presentation] IL-6, G-CSF 産生肺癌の一剖検例2017

    • Author(s)
      森田茂樹,古谷弦太,安藤純世,森正也
    • Organizer
      第75回日本病理学会関東支部学術集会
    • Related Report
      2017 Research-status Report

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

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