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Role of gastrointestinal stem cells and therapeutic application

Research Project

Project/Area Number 15J00069
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Gastroenterology
Research InstitutionThe Institute for Adult Diseases Asahi Life Foundation

Principal Investigator

崎谷 康佑  公益財団法人朝日生命成人病研究所, 附属病院消化器内科, 特別研究員(PD)

Project Period (FY) 2015-04-24 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords胃癌 / 幹細胞 / 胃がん / がん微小環境 / 神経成長因子 / 炎症 / 微小環境 / Mist1
Outline of Annual Research Achievements

2015年4月から2016年10月まで、コロンビア大学医学部消化器内科に留学し、胃がんの幹細胞とがんの微小環境に着目した研究を行った。2015年には、Mist1陽性細胞が胃体部の胃がんの起源となることを報告した。さらに、Mist1陽性細胞が前庭部の胃がんの起源となることを示し、その成果の一部を報告した。2016年10月に帰国後、前庭部のMist1陽性細胞が胃がんの治療標的となることに着目した研究を国内でも継続し、前庭部の炎症性シグナルとして知られるCXCR4/CXCL12シグナルを阻害すると、Mist1陽性細胞も阻害されるが、別の前庭部の幹細胞マーカーであるCCK2R陽性細胞が代償的に増加することを発見した。これらのことから、CXCR4/CXCL12シグナル阻害とCCK2Rに対する抗体医薬の併用が胃がんに効果的であると考え、その効果を示した(CXCR4-expressing Mist1(+) progenitors in the gastric antrum contribute to gastric cancer development. Oncotarget. 2017 Nov 10;8(67):111012-111025.)。

また、糖尿病と前癌病変の関係に着目した研究を行い、脂肪肝(Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan. J Int Med Res. 2017 Jun;45(3):1208-1220.)、逆流性食道炎(Decline in perception of acid regurgitation symptoms from gastroesophageal reflux disease in diabetes mellitus patients. PLoS One. 2018 Mar 15;13(3):e0194466.)について、生活習慣病との新たな知見を報告した。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (7 results)

All 2018 2017 2016 2015

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

  • [Journal Article] Decline in perception of acid regurgitation symptoms from gastroesophageal reflux disease in diabetes mellitus patients2018

    • Author(s)
      Sakitani Kosuke、Suzuki Nobumi、Ihara Sozaburo、Hirata Yoshihiro、Kawazu Shoji、Iwamoto Yasuhiko、Koike Kazuhiko
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 3 Pages: 0194466-0194466

    • DOI

      10.1371/journal.pone.0194466

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Decrease in <i>PSCA</i> expression caused by <i>Helicobacter pylori</i> infection may promote progression to severe gastritis2017

    • Author(s)
      Toyoshima Osamu、Tanikawa Chizu、Yamamoto Ryuta、Watanabe Hidenobu、Yamashita Hiroharu、Sakitani Kosuke、Yoshida Shuntaro、Kubo Michiaki、Matsuo Keitaro、Ito Hidemi、Koike Kazuhiko、Seto Yasuyuki、Matsuda Koichi
    • Journal Title

      Oncotarget.

      Volume: 9 Issue: 3 Pages: 3936-3945

    • DOI

      10.18632/oncotarget.23278

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CXCR4-expressing Mist1+ progenitors in the gastric antrum contribute to gastric cancer development.2017

    • Author(s)
      Sakitani K, Hayakawa Y, Deng H, Ariyama H, Kinoshita H, Konishi M, Ono S, Suzuki N, Ihara S, Niu Z, Kim W, Tanaka T, Liu H, Chen X, Tailor Y, Fox JG, Konieczny SF, Onodera H, Sepulveda AR, Asfaha S, Hirata Y, Worthley DL, Koike K, Wang TC.
    • Journal Title

      Oncotarget.

      Volume: Nov 10;8(67) Issue: 67 Pages: 111012-111012

    • DOI

      10.18632/oncotarget.22451

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan2017

    • Author(s)
      Sakitani Kosuke、Enooku Kenichiro、Kubo Hirokazu、Tanaka Akifumi、Arai Hisakatsu、Kawazu Shoji、Koike Kazuhiko
    • Journal Title

      J Int Med Res

      Volume: 45 Issue: 3 Pages: 1208-1220

    • DOI

      10.1177/0300060517707672

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling.2017

    • Author(s)
      Hayakawa Y, Sakitani K, Konishi M, Asfaha S, Niikura R, Tomita H, Renz BW, Tailor Y, Macchini M, Middelhoff M, Jiang Z, Tanaka T, Dubeykovskaya ZA, Kim W, Chen X, Urbanska AM, Nagar K, Westphalen CB, Quante M, Lin CS, Gershon MD, Hara A, Zhao CM, Chen D, Worthley DL, Koike K, Wang TC.
    • Journal Title

      Cancer Cell

      Volume: 31 Pages: 21-34

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.2015

    • Author(s)
      Hayakawa Y, Ariyama H, Stancikova J, Sakitani K et al.
    • Journal Title

      Cancer Cell

      Volume: 28(6) Issue: 6 Pages: 800-814

    • DOI

      10.1016/j.ccell.2015.10.003

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] Mist1 positive stem cells in the antrum serve as a cell-of-origin for gastric cancer with Apc loss2016

    • Author(s)
      Kosuke Sakitani
    • Organizer
      DDW 2016 San Diego
    • Place of Presentation
      米国San Diego
    • Year and Date
      2016-05-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

URL: 

Published: 2015-11-26   Modified: 2024-03-26  

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