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Characterization of Lgr5+ cells using a transposon-induced glioblastoma mouse model and identification of novel therapeutic targets

Research Project

Project/Area Number 25460488
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKyoto Pharmaceutical University (2014-2015)
愛知県がんセンター(研究所) (2013)

Principal Investigator

Nakata Susumu  京都薬科大学, 薬学部, 准教授 (80590695)

Co-Investigator(Kenkyū-buntansha) FUJITA Mitsugu  近畿大学医学部, 細菌学教室, 准教授 (40609997)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords癌幹細胞 / 脳腫瘍 / 膠芽腫 / Lgr5 / Wnt / Shh / がん幹細胞 / マウスモデル / LGR5 / マウス発癌モデル / 幹細胞マーカー
Outline of Final Research Achievements

The Sleeping Beauty transposon-induced glioblastoma model was successfully introduced in the Lgr5-eGFP transgenic mouse. Precise collections of the mouse glioblastoma tissues were feasible. Several lines of neurosphere culture using a neural stem cell culture system derived from the mouse glioblastoma tissues were established. Higher Lgr5 expression levels in the GFP positive fraction were confirmed. The observations that the Lgr5 positive cells exerted higher tumorigenicity in vivo indicated that the cancer stem cell properties were enriched in the Lgr5 positive glioblastoma cells. Global gene expression analysis was performed, which identified the shh-pathway as a signal activated in the Lgr5 positive population and higher expression of CDKNs in Lgr5 negative population. Furthermore, Gli2 was identified as an indispensible factor for the glioblastoma stem cells.

Report

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

    (21 results)

All 2015 2014 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (13 results) (of which Int'l Joint Research: 1 results) Book (2 results)

  • [Journal Article] Intimo-intimal intussusception: a rare form of common carotid artery dissection2015

    • Author(s)
      Fujita M, Shintai K, Nakata S, Maeda N, Hatano N, Seki Y
    • Journal Title

      J Vasc Interv Radiol.

      Volume: 26 Issue: 9 Pages: 1414-6

    • DOI

      10.1016/j.jvir.2015.06.015

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polycomb group protein Ezh2 regulates hepatic progenitor cell proliferation and differentiation in murine embryonic liver.2014

    • Author(s)
      Koike H, Ouchi R, Ueno Y, Nakata S, Obana Y, Sekine K, Zheng YW, Takebe T, Isono K, Koseki H, Taniguchi H.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 8 Pages: 0-2

    • DOI

      10.1371/journal.pone.0104776

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deficient HER3 expression in poorly-differentiated colorectal cancer cells enhances gefitinib sensitivity2014

    • Author(s)
      Nakata S, Tanaka H, Ito Y, Hara M, Fujita M, Kondo E, Kanemitsu Y, Yatabe Y and Nakanishi H
    • Journal Title

      International Journal of Oncology

      Volume: 45 Issue: 4 Pages: 1583-1593

    • DOI

      10.3892/ijo.2014.2538

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ring1B Promotes Hepatic Stem/Progenitor Cell Expansion via Simultaneous Suppression of Cdkn1a and Cdkn2a.2014

    • Author(s)
      Koike H, Ueno Y, Naito T, Shiina T, Nakata S, Ouchi R, Obana Y, Sekine K, Zheng YW, Takebe T, Isono K, Koseki H, Taniguchi H
    • Journal Title

      Hepatology

      Volume: 印刷中 Issue: 1 Pages: 323-333

    • DOI

      10.1002/hep.27046

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.2014

    • Author(s)
      Ruma IMW, Putranto EW, Kondo E, Watanabe R, Saito K, Inoue Y, Yamamoto K, Nakata S,Kaihata M, Murata H and Sakaguchi M.
    • Journal Title

      Int J Oncol.

      Volume: 45(1) Issue: 1 Pages: 209-18

    • DOI

      10.3892/ijo.2014.2397

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emerging role for leucine-rich repeat-containing G-protein-coupled receptors LGR5 and LGR4 in cancer stem cells.2014

    • Author(s)
      Nakata S, Phillips E, Goidts V
    • Journal Title

      Cancer Management and Research

      Volume: 6 Pages: 171-180

    • DOI

      10.2147/cmar.s57846

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 悪性神経膠腫におけるMET遺伝子発現の臨床的意義2015

    • Author(s)
      田崎貴之, 藤田貢, 奥田武司, 中田晋, 吉岡宏真, 加藤天美
    • Organizer
      第19回バイオ治療法研究会学術集会
    • Place of Presentation
      東京理科大学森戸記念館 (東京)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] Inhibition of ABCG2 enhances chemo-sensitivity of murine glioma stem cell-like cells and reduces chemokine-mediated tumorigenicity2015

    • Author(s)
      Mitsugu Fujita, Hiromasa Yoshioka, Takeshi Okuda, Susumu Nakata, Shin-ichi Miyatake, Amami Kato, Osamu Yoshie
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター (札幌)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腫瘍内M2マクロファージにおけるB7-H3およびB7-H5発現量は肺癌原発転移性脳腫瘍の発症と相関する2015

    • Author(s)
      藤田貢, 奥田武司, 中田晋, 菰原義弘, 加藤天美, 義江修
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場 (名古屋)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒトABCG4は、新しいタイプの薬物輸送体である2015

    • Author(s)
      三宅美月, 塚本めぐみ, 佐竹一紘, 中田晋, 石川智久, 中川大
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場 (名古屋)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] B7-H3 and B7-H5 in tumor-associated M2 macrophages correlate with brain metastasis formation of lung cancer2015

    • Author(s)
      Mitsugu Fujita, Takeshi Okuda, Susumu Nakata, Yoshihiro Komohara, Amami Kato, Osamu Yoshie
    • Organizer
      がん免疫療法・マクロファージ国際会議
    • Place of Presentation
      東京大学 伊藤国際学術センター (東京)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト ABCG4 はヒト ABCG2 とは異なるタイプの薬物輸送体である2015

    • Author(s)
      三宅美月, 塚本めぐみ, 佐竹一紘, 中田晋, 石川智久, 中川大
    • Organizer
      第135回日本薬学会年会
    • Place of Presentation
      KIITOホール (神戸)
    • Year and Date
      2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] COX-2 blockade suppresses brain metastasis by inhibiting M2 macrophage accumulation2014

    • Author(s)
      Fujita M, Miura R, Nakata S, Okuda T, Komohara Y, Kuzushima K, Kato A, Yoshie O
    • Organizer
      第32回日本脳腫瘍学会学術総会
    • Place of Presentation
      シェラトングランデホテル (東京)
    • Year and Date
      2014-11-30
    • Related Report
      2014 Research-status Report
  • [Presentation] Deficient HER3 expression in poorly-differentiated colorectal cancer cells affects sensitivity to gefitinib2014

    • Author(s)
      Nakata S, Ito Y, Kanemitsu Y, Kondo E, Nakanishi H
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Prophylactic COX-2 Inhibition Suppresses Brain Metastasis of Lung Cancer by Inhibiting Myeloid-Derived Suppressor Cells.2014

    • Author(s)
      Fujita M, Miura R, Nakata S, Okuda T, Komohara Y, Kuzushima K, Kato A, Yoshie O
    • Organizer
      The 104th Annual Meeting of the American Association of Cancer Research
    • Place of Presentation
      San Diego Convention Center (San Diego)
    • Year and Date
      2014-04-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Localization of repressive histone marks and target genes dynamically switch through murine hepatic differentiation

    • Author(s)
      中田晋, 上野康晴, 小池博之, 関根圭輔, 谷口英樹
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] COX-2 blockade immunologically suppresses brain metastasis of lung cancer

    • Author(s)
      藤田貢, 中田晋, 加藤天美, 義江修
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] Analysis of chemoradiotherapy resistance in the human pancreatic cancer stem cells

    • Author(s)
      星野早百合, 関根圭輔, 孫略, 中田晋, 寺崎哲也, 森永聡一郎, 宮城洋平, 遠藤格, 横瀬智之, 上野康晴, 倉田昌直, 谷口英樹
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトABCG2が細胞に賦与するタキサン系抗がん剤耐性は、ABCG2遺伝子上に存在する非同義一塩基多型によって異なる

    • Author(s)
      塚本めぐみ, 佐竹一紘, 田島靖浩, 中田晋, 石川智久, 中川 大
    • Organizer
      第134回 日本薬学会年会
    • Place of Presentation
      熊本市総合体育館(熊本)
    • Related Report
      2013 Research-status Report
  • [Book] LGR5 as a marker of in brain cancer; Biomarkers in Disease.2015

    • Author(s)
      Nakata S, Phillips E, Goidts V
    • Total Pages
      18
    • Publisher
      Springer Netherlands
    • Related Report
      2015 Annual Research Report
  • [Book] Lgr5 as a marker in brain cancer (Biomarkers in Cancer)2015

    • Author(s)
      Nakata S, Phillips E, Goidts V
    • Total Pages
      14
    • Publisher
      Springer
    • Related Report
      2014 Research-status Report

URL: 

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

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