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Studies on the functions of IL-34 and its therapeutic application for multiple melanoma-relative osteolytic disease

Research Project

Project/Area Number 17K09913
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionHokkaido University

Principal Investigator

Ishikawa Kozo  北海道大学, 遺伝子病制御研究所, 客員研究員 (20624795)

Co-Investigator(Kenkyū-buntansha) 清野 研一郎  北海道大学, 遺伝子病制御研究所, 教授 (20312845)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords多発性骨髄腫 / 骨溶解病変 / IL-34 / 破骨細胞形成 / 破骨細胞 / 骨溶解 / 骨破壊病変 / Osteoclastgenesis / 癌 / トランスレーショナルリサーチ / 免疫学
Outline of Final Research Achievements

Multiple myeloma (MM) is a hematological malignancy and causes debilitating osteolytic disease. Interleukin-34 (IL-34), a ligand of CSF-1 receptor, might contribute to osteoclast differentiation. In this study, we identified IL-34 as an osteoclastogenic cytokine accelerates osteolytic disease in MM, which was enhanced by proinflammatory cytokines or bone marrow stromal cells. MM-derived IL-34 promoted osteoclast formation from mouse BM cells in vitro. Silencing of Il34 by small interfering RNA impaired osteoclast formation in vitro and attenuated osteolytic disease in vivo. In BM aspirates from MM patients, the expression levels of IL-34 in CD138+ populations vary among patients. MM-derived IL-34 promoted osteoclast formation from human monocytes, which was reduced by a neutralizing antibody against IL-34.
Taken together, this study describes MM-derived IL-34 may enhance osteolysis and suggesting IL-34 as a potential therapeutic target on osteoclastogenesis in MM patient.

Academic Significance and Societal Importance of the Research Achievements

多発性骨髄腫は、高齢者の罹患率が高く骨破壊を主徴候とする造血器腫瘍の一つであるが、それに対する有効な治療薬が未だ開発されていない。我々は、腫瘍の増悪因子であるTAMの分化に関わり、幾つかの悪性腫瘍(肺癌、卵巣癌、腎臓癌など)の予後悪化への寄与が考えられるIL-34が、骨破壊病変に関与することを仮定し、実験系や臨床研究にて示した。このことは骨破壊病態に対する治療標的の開発として意義があると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (1 results)

  • [Journal Article] Interleukin-34 expression in ovarian cancer: a possible correlation with disease progression2020

    • Author(s)
      Endo H, Hama N, Baghdadi M, Ishikawa K
    • Journal Title

      Int Immunol.

      Volume: 32(3) Pages: 175-186

    • NAID

      120006980030

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A role for IL-34 in osteolytic disease of multiple myeloma2019

    • Author(s)
      Baghdadi Muhammad、Ishikawa Kozo、Nakanishi Sayaka
    • Journal Title

      Blood Advances

      Volume: 3 Issue: 4 Pages: 541-551

    • DOI

      10.1182/bloodadvances.2018020008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential anti-lymphoma effect of M-CSFR inhibitor in adult T-cell leukemia/lymphoma2018

    • Author(s)
      Yoshihiro Komohara,1,2) Osamu Noyori,3) Yoichi Saito,1) Hiroto Takeya,1) Muhammad Baghdadi,4) Fumihito Kitagawa,4) Naoki Hama,4) Kozo Ishikawa,4) Yutaka Okuno,5) Kisato Nosaka,5) Ken-ichiro Seino,4) Masao Matsuoka,5) and Shinya Suzu3)
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 58 Issue: 4 Pages: 152-160

    • DOI

      10.3960/jslrt.18034

    • NAID

      130007529824

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High co-expression of IL-34 and M-CSF correlates with tumor progression and poor survival in lung cancers.2018

    • Author(s)
      Baghdadi M, Endo H, Takano A, Ishikawa K, Kameda Y, Wada H, Miyagi Y, Yokose T, Ito H, Nakayama H, Daigo Y, Suzuki N, Seino KI.
    • Journal Title

      Sci Rep.

      Volume: 11;8(1) Issue: 1 Pages: 418-427

    • DOI

      10.1038/s41598-017-18796-8

    • NAID

      120006414003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhanced IL-34 expression in Nivolumab-resistant metastatic melanoma.2018

    • Author(s)
      Han N, Baghdadi M, Ishikawa K
    • Journal Title

      Inflammation and Regeneration

      Volume: 5 Issue: 1 Pages: 3-3

    • DOI

      10.1186/s41232-018-0060-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] IL-34 promotes osteoclast formation and enhances bone disease in multiple myeloma2017

    • Author(s)
      石川浩三
    • Organizer
      第21回日本がん免疫学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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