• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The role of bone marrow-derived cells and interleukin-17 in the mouse model of Helicobacter-infected gastric cancer

Research Project

Project/Area Number 23590919
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionKyushu University

Principal Investigator

TAKAISHI Shigeo  九州大学, 学内共同利用施設等, 准教授 (20596829)

Research Collaborator WANG Timothy C.  コロンビア大学, 医学部消化器内科, 教授
HAYAKAWA Yoku  コロンビア大学, 医学部消化器内科, 主任研究員
Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords胃発癌マウス / 胃前庭部上皮幹細胞 / Lgr5陽性細胞 / ガストリン/CCK2受容体 / プロガストリン / ヘリコバクター菌感染 / 発癌物質メチルニトロソウレア / CCK2受容体阻害薬YF476 / ガストリン/CCK2受容体 / 国際情報交換(アメリカ合衆国) / 国際情報交換、アメリカ合衆国 / 「国際情報交流、アメリカ合衆国」 / 国際情報交流、アメリカ合衆国
Outline of Final Research Achievements

We found that gastrin/CCK2-receptor (CCK2R) defines antral stem cells at position +4, which overlapped with an Lgr5 negative or low cell population but was distinct from typical antral Lgr5 high stem cells. Treatment with progastrin interconverts Lgr5 negative or low, CCK2R positive cells into Lgr5 high cells, increases CCK2R positive cell numbers and promotes gland fission and carcinogenesis in response to the chemical carcinogen MNU. Pharmacological inhibition or genetic ablation of CCK2R attenuated progastrin-dependent stem cell expansionand carcinogenesis.
In summary, CCK2R labels +4 antral stem cells that can be activated and expanded by progastrin, thus identifying one hormonal trigger for gastric stem cell interconversion and a potential target for gastric cancer chemoprevention and therapy.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (13 results)

All 2015 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (3 results) Book (2 results)

  • [Journal Article] CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis.2015

    • Author(s)
      Hayakawa Y, Jin G, Wang H, Chen X, Westphalen CB, Asfaha S, Renz BW, Ariyama H, Dubeykovskaya ZA, Takemoto Y, Lee Y, Muley A, Tailor Y, Chen D, Muthupalani S, Fox JG, Shulkes A, Worthley DL, Takaishi S, Wang TC.
    • Journal Title

      Gut

      Volume: 64(4) Issue: 4 Pages: 544-553

    • DOI

      10.1136/gutjnl-2014-307190

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Progastrin Promotes Antral Carcinogenesis and Gastric Stem Cell Function2013

    • Author(s)
      Yoku Hayakawa, Shigeo Takaishi, Guangchun Jin, Hiroshi Ariyama, Christoph B. Westphalen, Samuel Asfaha, Yagnesh H. Tailor, Wataru Shibata, Xiangdong Yang, Duan Chen, Mark T. Whary, Sureshkumar Muthupalani, James G. Fox, Arthur Shulkes, Timothy C. Wang
    • Journal Title

      Gastroenterology

      Volume: Vol. 144, Issue 5, Suppl. 1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The unfolded protein response is activated in Helicobacter-induced gastric carcinogenesis in a non-cell autonomous manner2013

    • Author(s)
      Baird M, Woon Ang P, Clark I, Bishop D, Oshima M, Cook MC, Hemmings C, Takaishi S, Worthley D, Boussioutas A, Wang TC, Taupin D.
    • Journal Title

      Laboratory Investigation

      Volume: 93(1) Issue: 1 Pages: 112-122

    • DOI

      10.1038/labinvest.2012.131

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] P53 gene mutation increases progastrin dependent colonic proliferation and colon cancer formation in mice2012

    • Author(s)
      Ramanathan V, Jin G, Westphalen CB, Whelan A, Dubeykovskiy A, Takaishi S, Wang TC.
    • Journal Title

      Cancer Investigation

      Volume: 30(4) Issue: 4 Pages: 275-286

    • DOI

      10.3109/07357907.2012.657814

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vivo analysis of mouse gastrin gene regulation in enhanced GFP-BAC transgenic mice.2011

    • Author(s)
      Takaishi S, Shibata W, Tomita H, Jin G, Yang X, Ericksen R, Dubeykovskaya Z, Asfaha S, Quante M, Betz KS, Shulkes A, Wang TC.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 300(2) Issue: 2 Pages: G334-G344

    • DOI

      10.1152/ajpgi.00134.2010

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth.2011

    • Author(s)
      Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takaishi S, Baik GH, Shibata W, Diprete B, Betz KS, Friedman R, Varro A, Tycko B, Wang TC.
    • Journal Title

      Cancer Cell

      Volume: 19(2) Issue: 2 Pages: 257-272

    • DOI

      10.1016/j.ccr.2011.01.020

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of gastric carcinogenesis by the hormone, gastrin, is mediated by suppression of TFF1 epigenetic silencing.2011

    • Author(s)
      Tomita H, Kawakami K, Minamoto T, et al
    • Journal Title

      Gastroenterology

      Volume: 140 (3) Issue: 3 Pages: 879-91

    • DOI

      10.1053/j.gastro.2010.11.037

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] IFN-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis.2011

    • Author(s)
      Tu SP, Quante M, Bhagat G, Takaishi S, Cui G, Yang XD, Muthuplani S, Shibata W, Fox JG, Pritchard DM, Wang TC.
    • Journal Title

      Cancer Research

      Volume: 71(12) Issue: 12 Pages: 4247-4259

    • DOI

      10.1158/0008-5472.can-10-4009

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Progastrin Promotes Antral Carcinogenesis and Gastric Stem Cell Function2013

    • Author(s)
      Hayakawa Y, Takaishi S, Jin G, Ariyama H, Westphalen CB, Asfaha S, Tailor Y, Shibata W, Yang X, Chen D, Whary MT, Muthupalani S, Fox JG, Shulkes A, Wang TC
    • Organizer
      Digestive Disease Week 2013
    • Place of Presentation
      アメリカ合衆国、フロリダ
    • Related Report
      2012 Research-status Report
  • [Presentation] Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche2011

    • Author(s)
      Takaishi S
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2011 Research-status Report
  • [Presentation] Progastrin Promotes Antral Carcinogenesis and Gastric Stem Cell Function

    • Author(s)
      Yoku Hayakawa, Shigeo Takaishi, Guangchun Jin, Hiroshi Ariyama, Christoph B. Westphalen, Samuel Asfaha, Yagnesh H. Tailor, Wataru Shibata, Xiangdong Yang, Duan Chen, Mark T. Whary, Sureshkumar Muthupalani, James G. Fox, Arthur Shulkes, Timothy C. Wang
    • Organizer
      Digestive Disease Week,
    • Place of Presentation
      Orange County Convention Center, FL, USA
    • Related Report
      2013 Research-status Report
  • [Book] G.I. Research 第20巻1号 総説「胃癌・大腸癌幹細胞」2012

    • Author(s)
      高石繁生
    • Total Pages
      6
    • Publisher
      先端医学社
    • Related Report
      2012 Research-status Report
  • [Book] 最新内科学、6章 内科疾患と腫瘍学、2 癌幹細胞2012

    • Author(s)
      高石繁生、赤司浩一
    • Publisher
      西村書店
    • Related Report
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi