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Microvesicle-mediated interaction between multiple myeloma cells and bone marrow stroma

Research Project

Project/Area Number 25461434
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionJichi Medical University

Principal Investigator

Furukawa Yusuke  自治医科大学, 医学部, 教授 (00199431)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords多発性骨髄腫 / 接着耐性 / 間質細胞 / Microvesicle / microRNA
Outline of Final Research Achievements

Multiple myeloma cells acquire the resistance to anti-cancer drugs via interaction with bone marrow stroma (cell adhesion-mediated drug resistance). In this study, we investigated the role of circulating microvescles (cMV) produced by myeloma cells in cell adhesion-mediated drug resistance. We isolated cMV from the co-culcture supernatant of myeloma cells and human bone marrow-derived stromal cells.We then extracted total RNA form cMV and subjected them to microRNA arrays, and found that myeloma-derived cMV was very rich in miR-155 and mir-135b. Functional studies revealed that the expression level of miR-155 was positively correlated with the sensitivity of myeloma cells to proteasome inhibitors. We are currently investigating the precise mechanisms by which miR-155 determines the sensitivity of myeloma cells to proteasome inhibitors.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2015 2014 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Remarks (1 results)

  • [Journal Article] Phosphorylation-mediated EZH2 Inactivation Promotes Drug Resistance in Multiple Myeloma.2015

    • Author(s)
      Kikuchi, J., Koyama, D., Wada, T., Izumi, T., Hofgaard, P.O., Bogen, B. and Furukawa, Y.
    • Journal Title

      The Journal of Clinical Investigation

      Volume: 125 Pages: 4375-4390

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Overexpression of the Shortest Isoform of Histone Demethylase LSD1 Primes Hematopoietic Stem Cells for Malignant Transformation.2015

    • Author(s)
      Wada, T., Koyama, D., Kikuchi, J., Honda, H. and Furukawa, Y.
    • Journal Title

      Blood

      Volume: 125 Pages: 3731-3746

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular Pathogenesis of Multiple Myeloma.2015

    • Author(s)
      Furukawa, Y. and Kikuchi, J.
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 20 Pages: 413-422

    • NAID

      40022340491

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Overexpression of the Shortest Isoform of Histone Demethylase LSD1 Primes Hematopoietic Stem Cells for Malignant Transformation.2015

    • Author(s)
      Wada, T., Koyama, D., Kikuchi, J., Honda, H. and Furukawa, Y.
    • Journal Title

      BLOOD

      Volume: 125 Pages: 0000-0000

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Proteasome inhibitors exert cytotoxicity and increase chemosensitivity via transcriptional repression of Notch1 in T-cell acute lymphoblastic leukemia.2014

    • Author(s)
      Koyama D, Kikuchi J, Hiraoka N, Wada T, Kurosawa H, Chiba S, and Furukawa Y.
    • Journal Title

      Leukemia

      Volume: in press Issue: 6 Pages: 1216-1226

    • DOI

      10.1038/leu.2013.366

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5.2014

    • Author(s)
      Tago K, Funakoshi-Tago M, Itoh H, Furukawa Y, Kikuchi J, Kato T, Suzuki K, Yanagisawa K
    • Journal Title

      Oncogene

      Volume: 未定 Issue: 3 Pages: 310-318

    • DOI

      10.1038/onc.2013.561

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Purine analog-like properties of bendamustine underlie rapid activation of DNA damage response and synergistic effects with pyrimidine analogues in lymphoid malignancies.2014

    • Author(s)
      Hiraoka N, Kikuchi J, Yamauchi T, Koyama D, Wada T, Uesawa M, Akutsu M, Mori S, Nakamura Y, Ueda T, Kano Y, Furukawa Y.
    • Journal Title

      Plos One

      Volume: 13 Issue: 3 Pages: e90675-e90675

    • DOI

      10.1371/journal.pone.0090675

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suitable drug combination with bortezomib for multiple myeloma under stroma-free conditions and in contact with fibronectin or bone marrow stromal cells.2014

    • Author(s)
      Kikuchi J, Koyama D, Mukai YH, and Furukawa Y.
    • Journal Title

      Int J Hematol

      Volume: in press Issue: 6 Pages: 726-736

    • DOI

      10.1007/s12185-014-1573-3

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Remarks]

    • URL

      http://www.jichi.ac.jp/stem/index.html

    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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