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Systemic generation of metastatic models of lung adenocarcinoma

Research Project

Project/Area Number 25670178
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionJichi Medical University

Principal Investigator

niki toshiro  自治医科大学, 医学部, 教授 (90198424)

Co-Investigator(Kenkyū-buntansha) YOSHIMOTO TAICHIRO  自治医科大学, 医学部, 講師 (20634166)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺癌 / 転移 / マウス
Outline of Final Research Achievements

In this study, we established a series of mouse models of lung cancer metastasis by intracardiac inoculation of lung adenocarcinoma cell lines harboring various driver mutations, such as EGFR, KRAS, ALK, and MET. We also generated subclones that has the ability to grow in suspended condition but reattach in ordinary culture, by long-term, 3-dimensional culture under low-bind culture conditions. These subclones, designated FL clones, exhibited highly metastatic potential as compared to parental cell lines. We further performed comprehensive genomic analysis of the cell lines (parental and FL cell lines) and identified metastasis-related genes that showed altered expression in FL cells vs. parental cells, and genomic regions amplified in FL cell lines. Thus, the metastatic models created in the present study would be a promising new resource to study the molecular mechanisms of lung cancer metastasis that develop under various genetic background.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (17 results)

All 2016 2015 2014 2013 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] Prolyl isomerase Pin1 promotes survival in EGFR-mutant lung adenocarcinoma cells with an epithelial-mesenchymal transition phenotype.2016

    • Author(s)
      Sakuma Y, Nishikiori H, Hirai S, Yamaguchi M, Yamada G, Watanabe A, Hasegawa T, Kojima T, Niki T, Takahashi H.
    • Journal Title

      Lab Invest.

      Volume: 96 Issue: 4 Pages: 391-398

    • DOI

      10.1038/labinvest.2015.155

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Frequent loss of the expression of multiple subunits of the SWI/SNF complex in large cell carcinoma and pleomorphic carcinoma of the lung.2015

    • Author(s)
      Yoshimoto T, Matsubara D, Nakano T, Tamura T, Endo S, Sugiyama Y, Niki T.
    • Journal Title

      Pathology international

      Volume: 35 Issue: 11 Pages: 595-602

    • DOI

      10.1111/pin.12350

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma2015

    • Author(s)
      Shin Saito, Kazue Morishima, Takashi Ui, Hiroko Hoshino, Daisuke Matsubara, Shumpei Ishikawa, Hiroyuki Aburatani, Masashi Fukayama, Yoshinori Hosoya, Naohiro Sato, Alan K Lefor, Yoshikazu Yasuda and Toshiro Niki
    • Journal Title

      BMC cancer

      Volume: 15 Issue: 1 Pages: 1-12

    • DOI

      10.1186/s12885-015-1065-8

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) synergizes with cisplatin and induces apoptosis in cisplatin-resistant esophageal squamous cell carcinoma cell lines via the Akt/XIAP pathway.2014

    • Author(s)
      Ui T, Morishima K, Saito S, Sakuma Y, Fujii H, Hosoya Y, Ishikawa S, Aburatani H, Fukayama M, Niki T, Yasuda Y.
    • Journal Title

      Oncol Rep.

      Volume: 31(2) Issue: 2 Pages: 619-24

    • DOI

      10.3892/or.2013.2899

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition.2014

    • Author(s)
      Ibrahim R, Matsubara D, Osman W, Morikawa T, Goto A, Morita S, Ishikawa S, Aburatani H, Takai D, Nakajima J, Fukayama M, Niki T, Murakami Y
    • Journal Title

      Hum Pathol.

      Volume: 45 Issue: 7 Pages: 1397-405

    • DOI

      10.1016/j.humpath.2014.02.013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stromal fibroblasts are predictors of disease-related mortality in esophageal squamous cell carcinoma.2014

    • Author(s)
      Saito S, Morishima K, Ui T, Matsubara D, Tamura T, Oguni S, Hosoya Y, Sata N, Lefor AT, Yasuda Y, Niki T.
    • Journal Title

      Oncology Reports

      Volume: 32 Issue: 1 Pages: 348-354

    • DOI

      10.3892/or.2014.3216

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemical analysis of the expression of E-cadherin and ZEB1 in non-small cell lung cancer.2014

    • Author(s)
      Matsubara D, Kishaba Y, Yoshimoto T, Sakuma Y, Sakatani T, Tamura T, Endo S, Sugiyama Y, Murakami Y, Niki T
    • Journal Title

      Pathology International

      Volume: 64 Issue: 11 Pages: 560-568

    • DOI

      10.1111/pin.12214

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lung cancer with loss of BRG1?BRM,shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features.2013

    • Author(s)
      Matsubara D, Murakami Y, Niki T et al.
    • Journal Title

      Cancer Sci

      Volume: 104 Issue: 2 Pages: 266-273

    • DOI

      10.1111/cas.12065

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced autophagy is required for survival in EGFR-independent EGFR-mutant lung adenocarcinoma cells.2013

    • Author(s)
      Sakuma Y, Matsukuma S, Nakamura Y, Yoshihara M, Koizume S, Sekiguchi H, Saito H, Nakayama H, Kameda Y, Yokose T, Oguni S, Niki T, and Miyagi Y.
    • Journal Title

      Lab Invest.

      Volume: 93 Issue: 10 Pages: 1137-1146

    • DOI

      10.1038/labinvest.2013.102

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] CADM1陽性の高悪性度肺腺癌におけるRAPGEF2の役割.2015

    • Author(s)
      許淑真,松原大祐,森川鉄平,中島淳,深山正久,仁木利郎,村上善則
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肺癌におけるYAP1 欠如と神経内分泌分化について2015

    • Author(s)
      松原大祐,伊東剛,田中一大,石川俊平,後藤悌,中野智之,土橋洋,中島淳,遠藤俊輔,深山正久,関戸好孝,仁木利郎,村上善則
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Altered expressions of multiple subunits of the switch/sucrose non-fermenting (SWI/SNF) complex in Non-small cell lung cancer.2015

    • Author(s)
      Yoshimoto T, Matsubara D, Niki T.
    • Organizer
      AACR special meeting
    • Place of Presentation
      Atlanta
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition.2014

    • Author(s)
      Matsubara D, Ibrahim R, Osman W, Goto A, Morikawa T, Morita S, Ishikawa S, Aburatani H, Fukayama M, Niki T, Murakami Y.
    • Organizer
      Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      San Diego
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Research-status Report
  • [Presentation] The HSP90 inhibitor 17-AAG improves chemoresistance of cisplatin-resistant esophageal squamous cell carcinoma cell lines.2014

    • Author(s)
      Ui T, Morishima K, Saito S, Sakuma Y, Fujii H, Hosoya Y, Yasuda Y, Niki T.
    • Organizer
      Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      San Diego
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Molecular mechanisms for EMT in lung cancer; relationship with chromatin remodeling factors and mutation of EGFR.2013

    • Author(s)
      Yoshimoto T, Niki T, Matsubara D.
    • Organizer
      72th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Research-status Report
  • [Presentation] RET融合遺伝子を有する肺腺癌細胞株の発見2013

    • Author(s)
      松原大祐、石川俊平、小原詩織、吉本多一郎、坂谷貴司、片岡寛章、村上善則、油谷浩幸、深山正久、仁木利郎.
    • Organizer
      日本病理学会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Remarks] 自治医科大学統合病理学部門ホームページ

    • URL

      http://www.jichi.ac.jp/pathol/

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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