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Identification of specific markers for cancer stem cells and anti-cancer therapy targeting cancer stem cells

Research Project

Project/Area Number 24659363
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKyoto University

Principal Investigator

CHIBA Tsutomu  京都大学, 医学(系)研究科(研究院), 教授 (30188487)

Co-Investigator(Kenkyū-buntansha) SENO Hiroshi  京都大学, 医学研究科, 講師 (90335266)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords癌幹細胞 / 組織幹細胞 / Hes1 / Dckl1 / 大腸ポリープ / 癌幹細胞治療 / 大腸癌 / 分子標的治療
Research Abstract

We examined effects of targeting Hes1 and Dcamkl1, possible cancer stem cell markers, on colonic cancer cells. Hes1-specific siRNAs significantly reduced growth of human colonic cancer cells. In addition, we also examined the effect of Hes1-siRNA to ApcMin mice. Finally, we obtained Dckl1-positive cells from both normal intestine and polyps of ApcMin mice by FACS sorting, and found several transcripts specifically expressed in Dcamkl1-positive tumor cells. The siRNAs or inhibitors specific for the molecules exclusively expressed in Dcamkl1-positive tumor cells inhibited tumor cell growth without affecting normal epithelial cells. These data suggested possible anti-cancer strategy targeting cancer stem cells without affecting normal tissue stem cells.

Report

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

    (40 results)

All 2014 2013 2012 Other

All Journal Article (12 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Invited: 2 results) Remarks (4 results)

  • [Journal Article] Deletion of nardilysin prevents the development of steatohepatitis and liver fibrosis.2014

    • Author(s)
      Ishizu-Higashi S, Seno H, Nishi E, Matsumoto Y, Ikuta K, Tsuda M, Kimura Y, Takada Y, Kimura Y, Nakanishi Y, Kanda K, Komekado H, Chiba T.
    • Journal Title

      Plos One

      Volume: 9 Issue: 5 Pages: e98017-e98017

    • DOI

      10.1371/journal.pone.0098017

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A model of liver carcinogenesis originating from hepatic progenitor cells with accumulation of genetic alterations.2014

    • Author(s)
      Soo Ki Kim, Akihiro Nasu, Junji Komori, Takahiro Shimizu, Yuko Matsumoto, Yasuko Minaki, Kenji Kohno, Kazuharu Shimizu, Shinji Uemoto, Tsutomu Chiba, Hiroyuki Marusawa.
    • Journal Title

      International Journal of Cancer

      Volume: 134 Issue: 5 Pages: 1067-76

    • DOI

      10.1002/ijc.28445

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics of hepatocellular carcinoma with stem/progenitor cell phenotypes.2014

    • Author(s)
      Lee M, Marusawa H, Chiba T
    • Journal Title

      Gastroenterology

      Volume: 146 Issue: 2 Pages: 579-581

    • DOI

      10.1053/j.gastro.2013.12.009

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Sox9-dependent acinar-to-ductal reprogramming is critical for neoplasia formation.2013

    • Author(s)
      Fukuda A, Chiba T
    • Journal Title

      Gastroenterology

      Volume: 145 Issue: 4 Pages: 904-907

    • DOI

      10.1053/j.gastro.2013.08.028

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] Heparan sulfate on intestinal epithelial cells plays a critical role in intestinal crypt homeostasis via Wnt/β-catenin signaling2013

    • Author(s)
      Yamamoto S, Nakase H, Matsuura M, Honzawa Y, Matsumura K, Uza N, Yamaguchi Y, Mizoguchi E, Chiba T
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 305 Issue: 3 Pages: G241-G249

    • DOI

      10.1152/ajpgi.00480.2012

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory Role of Gas6 in Intestinal Tumorigenesis.2013

    • Author(s)
      Yuki Nakanishi, et. al.
    • Journal Title

      Carcinogenesis

      Volume: (印刷中) Issue: 7 Pages: 1567-1574

    • DOI

      10.1093/carcin/bgt069

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dclk1 distinguishes between tumor and normal stem cells in the intestine.2013

    • Author(s)
      Yuki Nakanishi, et. al.
    • Journal Title

      Nature Genetics

      Volume: 45 Issue: 1 Pages: 98-103

    • DOI

      10.1038/ng.2481

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Morris JP 4th, Hebrok M. Bmi1 is required for regeneration of the exocrine pancreas in mice2012

    • Author(s)
      Fukuda A.
    • Journal Title

      Gastroenterology

      Volume: 143 Issue: 3 Pages: 821-831

    • DOI

      10.1053/j.gastro.2012.05.009

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of Hes genes in intestinaldevelopment, homeostasis and tumorformation2012

    • Author(s)
      Ueo T, Imayoshi T, Kobayashi T, OhtsukaT, Seno H, Nakae H, Chiba T, Kageyama R
    • Journal Title

      Development

      Volume: 139 Issue: 6 Pages: 1071-1082

    • DOI

      10.1242/dev.069070

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signaling via enhanced ectodomain shedding of TNF-a2012

    • Author(s)
      Kanda K, Komekado H, Kawada M, et al
    • Journal Title

      EMBO Molecular Medicine

      Volume: (印刷中) Issue: 5 Pages: 396-411

    • DOI

      10.1002/emmm.201200216

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer2012

    • Author(s)
      Kawada M, et al
    • Journal Title

      Oncogene

      Volume: (印刷中) Issue: 26 Pages: 3111-3123

    • DOI

      10.1038/onc.2011.498

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gastroesophageal reflux disease symptoms and dietary behaviors are significant correlates of short sleep duration in the general population : The Nagahama Study

    • Author(s)
      Murase K, Tabara Y, Takahashi Y, Muro S, Yamada R, Setoh K, Kawaguchi M, Kadotani H, Kosugi S, Sekine A, Nakayama T, Mishima M, Chiba T, Chin K, Matsuda F.
    • Journal Title

      Sleep

      Volume: (in press)

    • URL

      http://www.journalsleep.org/AcceptedPapers/SP-854-13.pdf

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Dclk1 discriminates between tumor and normal stem cells in the intestine2013

    • Author(s)
      妹尾浩、中西祐貴、千葉勉
    • Organizer
      シンポジウムがん幹細胞研究に基づく新たながん治療戦略第36回日本分子生物学会年会
    • Place of Presentation
      神戸神戸国際会議場
    • Year and Date
      2013-12-04
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸腫瘍幹細胞特異的マーカーDclk1の同定2013

    • Author(s)
      中西祐貴、上尾太郎、妹尾浩
    • Organizer
      International Sessionsがん幹細胞第72回日本癌学会総会
    • Place of Presentation
      横浜パシフィコ横浜
    • Year and Date
      2013-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Intestinal tumors are continuously renewed by Dclk1-positive tumor stem cells2013

    • Author(s)
      Nakanishi Y, Seno H, Chiba T.
    • Organizer
      American Association of Cancer Research, Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA, Walter E. Washington Convention Center
    • Year and Date
      2013-04-10
    • Related Report
      2013 Final Research Report
  • [Presentation] 正常腸管および腸腫瘍におけるDclk1/Lgr5陽性細胞の役割2013

    • Author(s)
      中西祐貴、妹尾浩、上尾太郎
    • Organizer
      第99回日本消化器病学会総会
    • Place of Presentation
      鹿児島かごしま県民交流センター
    • Year and Date
      2013-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Dclk1 discriminates between tumor and normal stem cells in the intestine2012

    • Author(s)
      Seno H.
    • Organizer
      GI Research Academy 2012
    • Place of Presentation
      Tokyo, Japan, Keidanren Hall
    • Year and Date
      2012-06-15
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸腫瘍幹細胞特異的マーカーDcamkl1の同定2012

    • Author(s)
      中西祐貴、上尾太郎、妹尾浩
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京京王プラザホテル
    • Year and Date
      2012-04-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Hes1は大腸上皮細胞の位置を規定し、ニッチ由来のWntやBMPシグナルによる分化制御に関与する2012

    • Author(s)
      上尾太郎、妹尾浩、仲瀬裕志
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京京王プラザホテル
    • Year and Date
      2012-04-19
    • Related Report
      2013 Final Research Report
  • [Presentation] The role of Dclk1-positive cells in the intestinal homeostasis. 2012 James W. Freston Single Topic Conference2012

    • Author(s)
      Nakanishi Y, Seno H, Ueo T, Chiba T.
    • Organizer
      Gastrointestinal Stem Cell Biology and Pathobiology
    • Place of Presentation
      Chicago, USA, Intercontinental Hotel Chicago
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍肝細胞による腫瘍組織構築機構の検討

    • Author(s)
      中西祐貴、妹尾 浩、千葉 勉
    • Organizer
      第50回日本臨床分子医学会学術集会・学術奨励賞
    • Place of Presentation
      東京国際フォーラム(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] DCLK1 is a specific marker for tumor stem cells in the intestine

    • Author(s)
      Tsutomu Chiba
    • Organizer
      DDW2013・Lecture session
    • Place of Presentation
      Orange County Convention Center(Orland, USA)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] The role of nardilysin in intestinal tumorigenesis

    • Author(s)
      Hiroshi Seno, Keitaro Kanda, Ei-ichiro Nishi, Tsutomu Chiba
    • Organizer
      GI Research Academy 2013
    • Place of Presentation
      Hotel Granvia Kyoto(Kyoto)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Naridilysin and ADAM protease promote gastric cancer cell growth by activating intrinsic cytokine signaling

    • Author(s)
      Tsutomu Chiba
    • Organizer
      SGCC 6th Anuual Scientific Meeting
    • Place of Presentation
      NUHS Tower Block Auditorium(Singapore)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Identification of Dclk1 as aspecific tumor stem cell marker in the intestine 腸腫瘍幹細胞マーカーDclk1の同定

    • Author(s)
      中西祐貴、妹尾 浩、上尾太郎、千葉 勉
    • Organizer
      第72回日本癌学会学術集会・International Sessions
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Nardilysin promotes gastric cancer growth by activating intrinsic cytokine signaling

    • Author(s)
      Keitaro Kanda, Yuto Kimura, Takuto Yoshioka, Hiroshi Seno, Tsutomu Chiba
    • Organizer
      The4th JCA-AACR Special conference
    • Place of Presentation
      Tokyo Bay Maihama Hotel Club & Resorts(Urayasu)
    • Related Report
      2013 Annual Research Report
  • [Presentation] がん幹細胞と正常組織幹細胞を区別する分子の同定

    • Author(s)
      千葉 勉
    • Organizer
      平成25年度文部科学省新学術領域研究 がん研究分野の特性等を踏まえた支援活動 公開シンポジウム
    • Place of Presentation
      一橋講堂(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腸腫瘍微小環境におけるナルディライジンの役割

    • Author(s)
      妹尾 浩、神田啓太郎、千葉 勉
    • Organizer
      平成25年度文部科学省新学術領域研究 がん研究分野の特性等を踏まえた支援活動 公開シンポジウム
    • Place of Presentation
      一橋講堂(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Hesは大腸上皮幹細胞の位置を規定し、ニッチ由来のWntやBMPシグナルによる分化制御に関与する

    • Author(s)
      上尾太郎
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] 腸腫瘍幹細胞特異的マーカーDcamkl1 の同定

    • Author(s)
      中西祐貴
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] Nardilysin はTNF-α のシェディングを促進し,腸炎を増悪させる

    • Author(s)
      神田啓太郎
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] Nardilysin maintains gastric cancer cell growth via promoting shedding of TNF-α and intrinsic cytokine signaling

    • Author(s)
      Keitaro Kanda
    • Organizer
      DDW2012
    • Place of Presentation
      San Diego Convention Center (San Diego, U.S.A.)
    • Related Report
      2012 Research-status Report
  • [Presentation] Genetic abolishment of hepatocyte proliferation activates hepatic stem cells.

    • Author(s)
      Yoko Endo
    • Organizer
      DDW2012
    • Place of Presentation
      San Diego Convention Center (San Diego, U.S.A.)
    • Related Report
      2012 Research-status Report
  • [Presentation] 肝細胞/前駆細胞への遺伝子異常の蓄積が肝癌の発生に果たす役割

    • Author(s)
      金 秀基
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市民文化会館(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] ナルディライジンはTNF-αのシェディングを促進し、マウス腸腫瘍を増大させる

    • Author(s)
      神田啓太郎
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市民文化会館(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] 脳幹・前駆細胞の活性化を介した新しい肝発癌モデルの樹立とその解析

    • Author(s)
      遠藤容子
    • Organizer
      JDDW2012 第54回日本消化器病学会大会
    • Place of Presentation
      ポートピアホテル(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Remarks] 1. JSPSホームページ科研費NEWS2013年度VOL1

    • URL

      http://www.jsps.go.jp/j-grantsinaid/22_letter/data/news_2013_vol1/p17.pdf

    • Related Report
      2013 Final Research Report
  • [Remarks] 2.京都大学ホームページ癌幹細胞を特定するマーカー同定に成功~新世代の癌治療法開発に期待~

    • URL

      http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2012/121203_1.htm

    • Related Report
      2013 Final Research Report
  • [Remarks] JSPS 科研費NEWS2013年度 VOL1

    • URL

      http://www.jsps.go.jp/j-grantsinaid/22_letter/data/news_2013_vol1/p17.pdf

    • Related Report
      2013 Annual Research Report
  • [Remarks] 京都大学ホームページ 癌幹細胞を特定するマーカー同定に成功 ~新世代の癌治療法開発に期待~

    • URL

      http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2012/121203_1.htm

    • Related Report
      2013 Annual Research Report

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

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