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Cancer stem cell for peritoneal metastasis in abdominal cavity

Research Project

Project/Area Number 24659600
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionThe University of Tokyo

Principal Investigator

ISHIGAMI Hironori  東京大学, 医学部附属病院, 講師 (80372382)

Co-Investigator(Kenkyū-buntansha) KITAYAMA Joji  東京大学, 医学部付属病院, 准教授 (20251308)
Co-Investigator(Renkei-kenkyūsha) YAMAGUCHI Hironori  東京大学, 医学部付属病院, 助教 (20376445)
YAMASHITA Hiroharu  東京大学, 医学部付属病院, 助教 (50599397)
YAZAWA Kentaro  東京大学, 医学部付属病院, 助教 (60572542)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腹膜播種 / 幹細胞 / フローサイトメトリー / 腹腔 / FACS
Research Abstract

We found that a minor subset of human intraperitoneal free cells with CD90+CD45- displayed the characteristics of mesenchymal stem cell, and differentiated into myofibroblast by the stimulation with TGFb, and intraperitoneal coinjection of with MKN45 significantly enhanced the rate of metastatic formation in the peritoneum of nude mice. Histological examination revealed that many MSC were engrafted in metastatic nodules and were mainly located at the fibrous area. Dasatinib, a tyrosine kinase inhibitor, strongly inhibited the proliferation of MSC but not MKN45 in vitro. Nevertheless, oral administration of Dasatinib significantly inhibited the development of peritoneal metastasis of MKN45, and resulted in reduced fibrillar formation of metastatic nodules. The rate of CD326+ tumor cells measured with FACS could be a reliable diagnostic biomarker to determine the severity of peritoneal metastasis as well as effectiveness of chemotherapy.

Report

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

    (12 results)

All 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment2014

    • Author(s)
      Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Watanabe T
    • Journal Title

      PLoS One

      Volume: 9(1)

    • Related Report
      2013 Final Research Report
  • [Journal Article] CD90(+)CD45(-) intraperitoneal mesothelial-like cells inhibit T cell activation by production of arginase I2014

    • Author(s)
      Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Yamashita H, Seto Y, Matsuzaki K, Watanabe T
    • Journal Title

      Cell Immunol

      Volume: 288(1-2) Pages: 8-14

    • Related Report
      2013 Final Research Report
  • [Journal Article] Intraperitoneal paclitaxel induces regression of peritoneal metastasis partly by destruction of peripheral microvessels2014

    • Author(s)
      Kitayama J,, Emoto S, Yamaguchi H, Ishigami H, Watanabe T
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 73(3) Pages: 605-12

    • Related Report
      2013 Final Research Report
  • [Journal Article] Flow cytometric quantification of intraperitoneal free tumor cells in patients with peritoneal metastasis2014

    • Author(s)
      Kitayama J,, Emoto S, Yamaguchi H, Ishigami H, Kamei T, Yamashita H, Seto Y, Matsuzaki K, Watanabe T
    • Journal Title

      Cytometry B Clin Cytom

      Volume: 86(1) Pages: 56-62

    • Related Report
      2013 Final Research Report
  • [Journal Article] CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment.2014

    • Author(s)
      Kitayama J
    • Journal Title

      PLoS One

      Volume: 21;9(1) Issue: 1 Pages: e86516-e86516

    • DOI

      10.1371/journal.pone.0086516

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD90(+)CD45(-) intraperitoneal mesothelial-like cells inhibit T cell activation by production of arginase I.2014

    • Author(s)
      Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Yamashita H, Seto Y, Matsuzaki K, Watanabe T.
    • Journal Title

      Cell Immunol

      Volume: 288 Issue: 1-2 Pages: 8-14

    • DOI

      10.1016/j.cellimm.2014.01.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment2014

    • Author(s)
      Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Watanabe T
    • Organizer
      104th Annual meeting of American Association of Cancer Research
    • Place of Presentation
      SanDiego CA, USA
    • Year and Date
      2014-04-06
    • Related Report
      2013 Final Research Report
  • [Presentation] 胃癌腹膜播種の成立における腹腔内遊離間葉系幹細胞の役割とその臨床的意義2014

    • Author(s)
      北山丈二、江本成伸、山口博紀、石神浩徳、渡邉聡明
    • Organizer
      第86回日本胃癌学
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 胃癌腹膜播種の成立における腹腔内遊離間葉系幹細胞の役割とその臨床的意義2014

    • Author(s)
      北山丈二
    • Organizer
      第86回日本胃癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of the intraperitoneal fibrocytes on the development of peritoneal metastasi2013

    • Author(s)
      北山丈二、江本成伸、山口博紀、石神浩徳、渡邉聡明
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of the intraperitoneal fibrocytes on the development of peritoneal2013

    • Author(s)
      北山丈二
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Remarks] HP

    • URL

      http://all-1su.umin.jp/surgical/

    • Related Report
      2013 Final Research Report

URL: 

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

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