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Analysis of microRNA regulating malignant potential of mammary tumor in the bone microenvironment.

Research Project

Project/Area Number 24501319
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionNagoya City University

Principal Investigator

FUTAKUCHI Mitsuru  名古屋市立大学, 医学(系)研究科(研究院), 准教授 (60275120)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords骨微小環境 / microRNA / がん幹細胞 / 微小環境 / 骨転移 / 動物モデル / 細胞増殖
Outline of Final Research Achievements

We set the hypothesis that cancer cells arrived at the bone microenvironment (bone ME), would survive with phenotype similar to cancer stem cells. We found that miR205 was down-regulated in the bone ME. miR205 overexpressing tumor cell lines (miR205+cells) were established and involvement of EMT was found. We also found that the drug sensitivity of inhibitors of ER, AR and HER2 were enhanced in miR205+cells. IHC study of SOX2, one of the cancer stem cell marker, revealed that SOX2+ cells were observed in the bone ME and that the number of SOX2+ cells was significantly lower than that of control after trasplant of miR205+ cells. Cathepsin D was regulated by miR205 in the tumor cells and whosehigh expression were correlated with clinical stage and T grade of TNM classification. Taken together, miR205 may be involved in the survival, induction of EMT, and drug resistance of the tumor cells in the bone ME, all of which are malignant phenotypes of clinically defined bone metastasis.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (43 results)

All 2014 2013 2012

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (24 results) (of which Invited: 8 results) Book (6 results)

  • [Journal Article] Nanosized zinc oxide particles do not promote DHPN-induced lung carcinogenesis but cause reversible epithelial hyperplasia of terminal bronchioles.2014

    • Author(s)
      Xu, J., Futakuchi, M., Alexander, D. B., Fukamachi, K., Numano, T., Suzui, M., Shimizu, H., Omori, T., Kanno, J., Hirose, A., and Tsuda, H.
    • Journal Title

      Archives of toxicology

      Volume: 88 Issue: 1 Pages: 65-75

    • DOI

      10.1007/s00204-013-1086-5

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes.2014

    • Author(s)
      Xu, J., Alexander, D. B., Futakuchi, M., Numano, T., Fukamachi, K., Suzui, M., Omori, T., Kanno, J., Hirose, A., and Tsuda, H.
    • Journal Title

      Cancer Sci

      Volume: 105 Issue: 7 Pages: 763-769

    • DOI

      10.1111/cas.12437

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Comparative study of toxic effects of anatase and rutile type nanosized titanium dioxide particles in vivo and in vitro.2014

    • Author(s)
      Numano, T., Xu, J., Futakuchi, M., Fukamachi, K., Alexander, D. B., Furukawa, F., Kanno, J., Hirose, A., Tsuda, H., and Suzui, M.
    • Journal Title

      Asian Pacific J Cancer Prev

      Volume: 15 Pages: 929-935

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Rat N-ERC/mesothelin as a marker for in vivo screening of drugs against pancreas cancer2014

    • Author(s)
      Fukamachi K, Iigo M, Hagiwara Y, Shibata K, Futakuchi M, Alexander DB, Hino O, Suzui M, Tsuda H.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 10 Pages: 268-274

    • DOI

      10.1371/journal.pone.0111481

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Murine Herc6 Plays a Critical Role in Protein ISGylation In Vivo and Has an ISGylation-Independent Function in Seminal Vesicles.2014

    • Author(s)
      Arimoto KI, Hishiki T, Kiyonari H, Abe T, Cheng C, Yan M, Fan JB, Futakuchi M, Tsuda H, Murakami Y, Suzuki H, Zhang DE, Shimotohno K
    • Journal Title

      J Interferon Cytokine Res.

      Volume: 35 Issue: 5 Pages: 351-358

    • DOI

      10.1089/jir.2014.0113

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel reporter rat strain that expresses LacZ upon Cre-mediated recombination2013

    • Author(s)
      Fukamachi K., Tanaka H., Sakai Y., Alexander D.B., Futakuchi M., Tsuda H., Suzui M.
    • Journal Title

      Genesis

      Volume: 51 Issue: 4 Pages: 268-274

    • DOI

      10.1002/dvg.22371

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Animal model of lung metastasis of hepatocellular carcinoma; A tool for the development of anti- metastatic therapeutics.2013

    • Author(s)
      M. Futakuchi
    • Journal Title

      Journal of Cancer Therapy

      Volume: 4 Issue: 02 Pages: 420-425

    • DOI

      10.4236/jct.2013.42a051

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Animal model for mammary tumor growth in the bone microenvironment.2013

    • Author(s)
      M. Futakuchi, R.K. Singh.
    • Journal Title

      Breast cancer (Tokyo, Japan)

      Volume: 20 Issue: 3 Pages: 195-203

    • DOI

      10.1007/s12282-013-0439-5

    • NAID

      10031202698

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Promotive effects of cell proliferation and chromosomal instability induced by tribbles-related protein 3 in mouse mammary tumor cells.2013

    • Author(s)
      Y. Sakai, K. Fukamachi, M. Futakuchi, H. Hayashi, M. Suzui.
    • Journal Title

      Oncology reports

      Volume: 30 Issue: 1 Pages: 64-70

    • DOI

      10.3892/or.2013.2441

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inflammatory Activation after Experimental Cardiac Tamponade2013

    • Author(s)
      Vass A, Süveges G, Erces D, Nógrády M, Varga G, Földesi I, Futakuchi M, Imai M, Okada N, Okada H, Boros M, Kaszaki J
    • Journal Title

      Eur Surg Res

      Volume: 51 Issue: 1-2 Pages: 1-13

    • DOI

      10.1159/000352089

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats.2012

    • Author(s)
      J. Xu, M. Futakuchi, H. Shimizu, D.B. Alexander, K. Yanagihara, K. Fukamachi, M. Suzui, J. Kanno, A. Hirose, A. Ogata, Y. Sakamoto, D. Nakae, T. Omori, H. Tsuda.
    • Journal Title

      Cancer Science

      Volume: 103 Issue: 12 Pages: 2045-2050

    • DOI

      10.1111/cas.12005

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice.2012

    • Author(s)
      A. Takagi, A. Hirose, M. Futakuchi, H. Tsuda, J. Kanno
    • Journal Title

      Cancer Science

      Volume: 103 Issue: 8 Pages: 1440-1444

    • DOI

      10.1111/j.1349-7006.2012.02318.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lack of promoting effect of titanium dioxide particles on chemically-induced skin carcinogenesis in rats and mice.2012

    • Author(s)
      Y. Sagawa, M. Futakuchi, J. Xu, K. Fukamachi, Y. Sakai, Y. Ikarashi, T. Nishimura, M. Suzui, H. Tsuda, A. Morita.
    • Journal Title

      The Journal of toxicological sciences

      Volume: 37 Pages: 317-327

    • NAID

      10030126738

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 骨転移巣を形成するがん細胞の悪性形質を規定するメカニズム2014

    • Author(s)
      二口 充
    • Organizer
      第28回骨代謝セミナー
    • Place of Presentation
      ホテル椿山荘(東京都文京区)
    • Year and Date
      2014-12-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 骨微小環境における乳がん細胞の増殖に関与するmicroRNAの同定とその機能解析2014

    • Author(s)
      二口 充, 深町勝己, 酒々井眞澄
    • Organizer
      第23回日本がん転移学会学術総会
    • Place of Presentation
      金沢市文化ホール(石川県金沢市)
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 骨微小環境におけるがん細胞の増殖メカニズム2014

    • Author(s)
      二口 充
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Growth of malignant tumor in the bone microenvironment.2014

    • Author(s)
      Futakuchi, M.
    • Organizer
      2014 Seoul National University Cancer Research Institute,
    • Place of Presentation
      Mokpo, Korea
    • Year and Date
      2014-04-16 – 2014-04-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 骨微小環境における腫瘍細胞増殖メカニズム:動物モデルを用いた解析.2014

    • Author(s)
      二口充
    • Organizer
      平成25年度「個体レベルでのがん支援活動」ワークショップ
    • Place of Presentation
      琵琶湖ホテル(琵琶湖)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] A rat model of preclinical diagnosis of lung carcinoma.2013

    • Author(s)
      K. Fukamachi, Y. Ohshima, M. Futakuchi, H. Tsuda, M. Suzui.
    • Organizer
      72nd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] Growth of malignant tumor in the bone microenvironment; mechanism of bone metastasis and its therapeutic targets.2013

    • Author(s)
      M. Futakuchi, K. Fukamachi, M. Suzui.
    • Organizer
      72nd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] GROWTH OF MALIGNANT TUMOR IN THE BONE MICROENVIRONMENT.2013

    • Author(s)
      M. Futakuchi.
    • Organizer
      The 18th Korea- Japan Cancer Research Workshop 2013;
    • Place of Presentation
      岐阜都ホテル(岐阜)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 骨微小環境における前立腺癌および乳癌の増殖メカニズムに着目した骨転移治療薬の開発と展開.2013

    • Author(s)
      二口充
    • Organizer
      第24回新薬創製懇話会
    • Place of Presentation
      ニューウエルサンピア沼津(沼津)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 骨微小環境における乳がん細胞の増殖と溶骨性変化を制御するRANKL-RANKシグナルの関連.2013

    • Author(s)
      二口充, 坂井勇斗, 深町勝巳, 酒々井眞澄.
    • Organizer
      第102回日本病理学会
    • Place of Presentation
      札幌芸文館(札幌)
    • Related Report
      2013 Research-status Report
  • [Presentation] ナノ材料の噴霧曝露後、長期間経過して発生するリスクの背景となる肺組織の検索.2013

    • Author(s)
      二口充, 徐結苟, 深町勝巳, 津田洋幸, 酒々井眞澄.
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2013 Research-status Report
  • [Presentation] 骨微小環境における腫瘍間質相互作用のメカニズム:前立腺がんおよび乳がんを用いた動物モデルによる解析.2013

    • Author(s)
      二口充, 深町勝巳, 酒々井眞澄.
    • Organizer
      第22回日本がん転移学会
    • Place of Presentation
      ホテルビエノビスタ松本(松本)
    • Related Report
      2013 Research-status Report
  • [Presentation] Krasトランスジェニックラット膵管がんモデルにおける画像診断の試み2013

    • Author(s)
      柴田耕治, 辻厚至, 深町勝巳, 二口充, 津田洋幸, 酒々井眞澄
    • Organizer
      平成24年度「個体レベルでのがん支援活動」ワークショップ
    • Place of Presentation
      琵琶湖ホテル、大津
    • Related Report
      2012 Research-status Report
  • [Presentation] パルミチン酸誘導体のインビトロ、インビボ抗がん効果の検討および作用機序のインシリコ解析.2013

    • Author(s)
      礒田泰彰, 森脇健太, 坂井勇斗, 深町勝巳, 二口充, 酒々井眞澄
    • Organizer
      平成24年度「個体レベルでのがん支援活動」ワークショップ
    • Place of Presentation
      琵琶湖ホテル、大津
    • Related Report
      2012 Research-status Report
  • [Presentation] パルミチン酸誘導体の抗がん効果の検証2013

    • Author(s)
      酒々井眞澄, 坂井勇斗, 深町勝巳, 二口充, 礒田泰彰, 森脇健太
    • Organizer
      平成24年度「個体レベルでのがん支援活動」ワークショップ
    • Place of Presentation
      琵琶湖ホテル、大津
    • Related Report
      2012 Research-status Report
  • [Presentation] Reactive Pulmonary Hyperplasia Induced by Intra Pulmonary Spray of Nano-Sized Carbon Black Particles.2012

    • Author(s)
      M. Futakuchi, J. Xu, Y. Inoue, M. Takatsuki, H. Tsuda, S. Masumi.
    • Organizer
      The 6th International Congress of Asian Society of Toxicology
    • Place of Presentation
      Sendai International Center, Sendai
    • Related Report
      2012 Research-status Report
  • [Presentation] Malignant tumor growth in the bone microenvironment; crosstalk between TGFβ and ERK/AKT/PTEN signaling pathway.2012

    • Author(s)
      M. Futakuchi, Y. Sakai, K. Fukamachi, R.K. Singh, M. Suzui.
    • Organizer
      The 14th international Binnial Congress of the Metastasis Research Society
    • Place of Presentation
      Brisbane, Austlaria
    • Related Report
      2012 Research-status Report
  • [Presentation] SUPPRESSION OF METASTASIS BY NUCLEAR FACTOR KAPPAB INHIBITORS IN AN IN VIVO LUNG METASTASIS MODEL OF CHEMICALLY INDUCED HEPATOCELLULAR CARCINOMA.2012

    • Author(s)
      M. Futakuchi, K. Fukamachi, M. Suzui.
    • Organizer
      The 17th Japan-Korea Cancer Research Workshop
    • Place of Presentation
      Busan, Korea
    • Related Report
      2012 Research-status Report
  • [Presentation] Tumor growth in the bone microenvironment ; crosstalk between TGFbeta and ERK/AKT/PTEN signaling pathway.2012

    • Author(s)
      M. Futakuchi, Y. Sakai, K. Fukamachi, M. Suzui.
    • Organizer
      71th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Royton Sapporo, Sapporo
    • Related Report
      2012 Research-status Report
  • [Presentation] TRB3 gene increases cell proliferation in mouse mammary carcinoma cells.2012

    • Author(s)
      Y. Sakai, K. Fukamachi, M. Futakuchi, H. Hayashi, M. Suzui.
    • Organizer
      71th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Royton Sapporo,o Sapporo
    • Related Report
      2012 Research-status Report
  • [Presentation] がんの骨転移の予防:可溶性Receptor Activator of Nuclear factor-kB Ligand (RANKL) を標的とした骨微小環境における乳がん細胞の増殖の予防作用.2012

    • Author(s)
      二口充, 坂井勇斗, 深町勝巳, 酒々井真澄.
    • Organizer
      がん予防大会2012
    • Place of Presentation
      じゅうろくプラザ、岐阜
    • Related Report
      2012 Research-status Report
  • [Presentation] Crosstalk between TGFbeta and MAPK/AKT/PTEN signaling pathway in the bone microenvironment2012

    • Author(s)
      M. Futakuchi, K. Fukamachi, M. Suzui
    • Organizer
      第21回日本癌転移学会学術集会
    • Place of Presentation
      オリエンタルホテル広島、広島
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨微小環境におけるTGFβのシグナル伝達とAKT/PTEN、MAPKおよびRANKLシグナルとの関連.2012

    • Author(s)
      二口充, 坂井勇斗, 深町勝巳, 酒々井真澄.
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      京王プラザホテル、東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨微小環境での腫瘍間質相互作用における可溶性RANKLとTGFβの役割:前立腺癌・乳癌を用いた動物モデルによる解析2012

    • Author(s)
      二口充
    • Organizer
      第58回日本病理学会秋期特別総会
    • Place of Presentation
      ウインク愛知、名古屋
    • Related Report
      2012 Research-status Report
  • [Book] がん細胞と転移標的臓器の微小環境について, 癌と微小環境, Surgery Frontier2014

    • Author(s)
      二口 充
    • Total Pages
      6
    • Publisher
      Surgical Frontier, メディカルレビュー社
    • Related Report
      2014 Annual Research Report
  • [Book] 骨転移のメカニズム 骨微小環境における腫瘍間質相互作用, がん転移の機構2014

    • Author(s)
      二口 充
    • Total Pages
      4
    • Publisher
      Medical Scidence Digest, ニューサイエンス社
    • Related Report
      2014 Annual Research Report
  • [Book] 癌骨転移のメカニズム, 悪性腫瘍と骨•カルシウム2014

    • Author(s)
      二口 充
    • Total Pages
      7
    • Publisher
      Clinical Calcium, 医薬ジャーナル社
    • Related Report
      2014 Annual Research Report
  • [Book] 浸潤と転移, 新臨床腫瘍学(改訂第4版)がん薬物療法専門医のために2014

    • Author(s)
      二口 充
    • Total Pages
      3
    • Publisher
      南江堂
    • Related Report
      2014 Annual Research Report
  • [Book] 遺伝子医学MOOK22号 前立腺がんおよび乳がんの骨浸潤モデル:骨微小環境における腫瘍間質相互作用の分子メカニズムの解明と骨転移治療薬の開発への応用2012

    • Author(s)
      二口 充
    • Total Pages
      270
    • Publisher
      株式会社 メディカル ドゥ
    • Related Report
      2012 Research-status Report
  • [Book] 疾患モデルの作成と利用 ーがんー(編集:中村卓郎) 第3節転移浸潤モデル 第3項骨浸潤モデル2012

    • Author(s)
      二口 充
    • Total Pages
      633
    • Publisher
      株式会社 エル アイ シー
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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