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Role of bone-marrow derived mesenchymal stem cells in growth and metastasis of colon cancer.

Research Project

Project/Area Number 21590813
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

KITADAI Yasuhiko  広島大学, 大学院・医歯薬学総合研究科, 准教授 (10304437)

Co-Investigator(Renkei-kenkyūsha) SHINAGAWA Kei  広島大学, 病院, 医科診療医 (50623609)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords下部消化管学(小腸、大腸) / 骨髄由来間葉系幹細胞 / 間質 / 癌転移 / 分子標的治療 / MSC / CAF / 大腸癌 / Mesenchymal stem cell (MSC) / Carcinoma-associated fibroblast (CAF) / Colon cancer / Metastasis
Research Abstract

In an orthotopic nude mice model of colon cancer, mesenchymal stem cells(MSCs) traveled to tumor stroma, where they differentiated into carcinoma-associated fibroblast(CAF)-like cells. The KM12SM+ MSC xenograft enhanced cell proliferation and angiogenesis and inhibited tumor cell apoptosis. When tumor-bearing animals were treated with imatinib, there was no significant increase in primary tumor volume or total volume of liver metastases, despite the KM12SM+ MSC xenograft, and survival in the mixed-cell group was prolonged by imatinib treatment. Moreover, the ability of MSCs to migrate to tumor stroma was impaired, and the number of MSCs surviving in the tumor microenvironment was significantly decreased. Our data suggest that blockade of PDGF signaling pathways influences the interaction between bone marrow-derived MSCs and tumor cells in the tumor microenvironment and, hence, inhibits the progressive growth of colon cancer.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (22 results)

All 2012 2011 2010 2009

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (8 results) Book (4 results)

  • [Journal Article] Stroma-directed molecular targeted therapyin gastric cancer2011

    • Author(s)
      Kitadai, Y., Kodama, M., Shinagawa, K.
    • Journal Title

      Cancers

      Volume: 3 Pages: 4245-4057

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-stromal therapy with imatinib inhibits growth and metastasis of gastric carcinoma in an orthotopic nude mouse model2011

    • Author(s)
      Sumida, T., Kitadai, Y., Shinagawa, K., Tanaka, M., Kodama, M., Ohnishi, M., Ohara, E., Tanaka, S., Yasui, W., Chayama, K.
    • Journal Title

      Int J Cancer

      Volume: 128 Pages: 2050-2062

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stroma-directed molecular targeted therapy in gastric cancer2011

    • Author(s)
      Kitadai, Y., Kodama, M., Shinagawa, K
    • Journal Title

      Cancers, 3

      Volume: 3 Pages: 4245-4257

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiogenesis and lymphangiogenesis of gastric cancer2010

    • Author(s)
      Kitadai, Y.
    • Journal Title

      J. Oncol. 2010

      Volume: Article ID 468725

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of platelet-derivedgrowth factor(PDGF)-B and PDGF-receptor beta is associated with lymphatic metastasis in human gastric carcinoma2010

    • Author(s)
      Kodama, M., Kitadai, Y., Sumida, T., Ohnishi, M., Ohara, E., Tanaka, M., Shinagawa, K., Tanaka, S., Yasui, W., Chayama, K.
    • Journal Title

      Cancer Sci

      Volume: 101 Pages: 1984-1989

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cells enhance growthand metastasis of colon cancer2010

    • Author(s)
      Shinagawa, K., Kitadai, Y., Tanaka, M., Sumida, T., Kodama, M., Higashi, Y., Tanaka, S., Yasui, W., Chayama, K.
    • Journal Title

      Int J Cancer

      Volume: 127 Pages: 2323-2333

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potential rolefor vascular endothelial growth factor-D asan autocrine factor for human gastric carcinoma cells2010

    • Author(s)
      Tanaka, M., Kitadai, Y., Kodama, M., Shinagawa, K. Sumida, T., Tanaka, S., Oue, N., Yasui, W., Chayama, K.
    • Journal Title

      Cancer Sci

      Volume: 101 Pages: 2121-2127

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cells enhance growth and metastasis of colon cancer.2010

    • Author(s)
      Shinagawa, K., Kitadai, Y., et al
    • Journal Title

      Int J Cancer

      Volume: 127 Pages: 2323-2333

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cancer-stromal cell interaction and tumor angiogenesis in gastric cancer2009

    • Author(s)
      Kitadai, Y.
    • Journal Title

      Cancer Microenviron. Epub

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer-stromal cell interaction and tumor angiogenesis in gastric cancer2009

    • Author(s)
      Kitadai Y.
    • Journal Title

      Cancer Microenviron Epub

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Blockade of PDGFR signaling with imatinib inhibits lymph node metastasis ofgastric carcinoma in an orthotopic nudemouse model2011

    • Author(s)
      Kitadai, Y., Kodama, M., Sumida, T., Shinagawa, K., Tanaka, S., Chayama, K.
    • Organizer
      Montreal International Symposium on Angiogenesis and Metastasis (MISAM)
    • Place of Presentation
      Montreal, Quebec, Canada
    • Year and Date
      2011-06-15
    • Related Report
      2011 Final Research Report
  • [Presentation] Blockade ofPDGFR signaling impairs the tumorpromoting effect of bone marrow-derivedmesenchymal stem cells in colon cancer2011

    • Author(s)
      Shinagawa, K., Kitadai, Y., Ohnishi, M., Ohara, E., Tanaka, M., Sumida, T., Tanaka, S., Yasui, W., Chayama, K.
    • Organizer
      102st Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Orland, FL, USA,
    • Related Report
      2011 Final Research Report
  • [Presentation] Blockade of PDGFR signaling impairs the tumor promoting effect of bone marrow-derived mesenchymal stem cells in colon cancer2011

    • Author(s)
      Shinagawa, K., Kitadai, Y., et al
    • Organizer
      102st Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Orland, FL, USA
    • Related Report
      2011 Annual Research Report
  • [Presentation] Blockade of PDGFR signaling with imatinib inhibits lymph node metastasis of gastric carcinoma in an orthotopic nude mouse model2011

    • Author(s)
      Kitadai, Y., Kodama, M., et al
    • Organizer
      Montreal International Symposium on Angiogenesis and Metastasis (MISAM)
    • Place of Presentation
      Montreal, Quebec, Canada
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tumor-stroma interaction in gastrointestinal cancers.2010

    • Author(s)
      Kitadai, Y.
    • Organizer
      Seminar, New York Medical College
    • Place of Presentation
      New York, USA(招待講演)
    • Year and Date
      2010-04-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Significance of mesenchymal stem cells in growth and metastasis of colon cancer.2010

    • Author(s)
      Shinagawa, K., Kitadai, Y., et al
    • Organizer
      101st Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Washington D.C., USA
    • Year and Date
      2010-04-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] Significance of mesenchymal stem cells in growth and metastasis of colon cancer2010

    • Author(s)
      Shinagawa, K., Kitadai, Y., Tanaka, M., Sumida, T., Kodama, M., Tanaka, S., Yasui, W., Chayama, K.
    • Organizer
      101st Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Washington D.C., USA
    • Year and Date
      2010-04-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Blockade of PDGFRsignaling impairs the tumor promotingeffect of bone marrow-derivedmesenchymal stem cells in colon cancer2010

    • Author(s)
      Kitadai, Y., Shinagawa, K., Tanaka, M., Sumida, T., Kodama, M., Tanaka, S., Yasui, W., Chayama, K.
    • Organizer
      Joint Metastasis Research Society-AAC Rconference
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2011 Final Research Report
  • [Book] Enhancedgrowth and metastasis of colon cancer : Roleof mesenchymal stem cells. Stem Cells andCancer Stem Cells2012

    • Author(s)
      Kitadai, Y., Shinagawa, K
    • Publisher
      TherapeuticApplications in Disease and Injury
    • Related Report
      2011 Final Research Report
  • [Book] Enhanced growth and metastasis of colon cancer : Role of mesenchymal stem cells.Stem Cells and Cancer Stem Cells : Therapeutic Applications in Desease and Injury, Volume 4 (Hayat, M.A., ed)2012

    • Author(s)
      Kitadai, Y., Shinagawa, K.
    • Publisher
      Springer, USA(in press)
    • Related Report
      2011 Annual Research Report
  • [Book] Regulation of lymphangiogenesis in human gastric cancer2011

    • Author(s)
      Kitadai, Y., Kodama, M
    • Publisher
      Trends in Cancer Research, Volume
    • Related Report
      2011 Final Research Report
  • [Book] Regulation of lymphangiogenesis in human gastric cancer. Trends in Cancer Research, Volume 72011

    • Author(s)
      Kitadai, Y., Kodama, M.
    • Total Pages
      7
    • Publisher
      Research Trends, India
    • Related Report
      2011 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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