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Roles of bone metastatic mammary tumor cell-derived extracellular vesicles in osteoclast differentiation and function

Research Project

Project/Area Number 15K11014
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphological basic dentistry
Research InstitutionKyushu University

Principal Investigator

Uehara Norihisa  九州大学, 歯学研究院, 助教 (30368211)

Co-Investigator(Kenkyū-buntansha) 久本 由香里  九州大学, 歯学研究院, 助教 (40729026)
久木田 明子  佐賀大学, 医学部, 准教授 (30153266)
久木田 敏夫  九州大学, 歯学研究院, 教授 (70150464)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords癌骨転移 / 乳癌 / 細胞外小胞 / 破骨細胞 / miRNA / 骨転移 / 骨芽細胞
Outline of Final Research Achievements

The interplay between breast cancer cells and bone cells in bone marrow microenvironments play an important role in tumor progression through the secreting factors. Although extracellular vesicles (EVs) released from cancer cells have shown to regulate the many types of cancer progression, In this study, we explored the implications of bone metastatic breast cancer cell-derived EVs in the regulation of osteoclast differentiation, resorption and survival. Treatment of mouse bone marrow macrophages (BMMs) cells with mouse bone metastatic (4T1 and 4T1.2) mammary tumor cell-derived EVs (BM-EVs) promoted osteoclast differentiation. Treatment of mature osteoclasts with BM-EVs markedly increased bone resorption. Interestingly, BM-EVs attenuated apoptosis of osteoclasts through negative regulation of Bim and Caspase-3 activation. Taken together, our results demonstrate the implication of BM-EVs-mediated osteoclast formation, bone resorption and cell survival.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2018 2017 2016

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

  • [Journal Article] Osteoblast-derived Laminin-332 is a novel negative regulator of osteoclastogenesis in bone microenvironments.2017

    • Author(s)
      Uehara N, Kukita A, Kyumoto-Nakamura Y, Yamaza T, Yasuda H, Kukita T.
    • Journal Title

      Lab Invest.

      Volume: 97 Issue: 10 Pages: 1235-1244

    • DOI

      10.1038/labinvest.2017.55

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 骨転移癌細胞―破骨細胞間コミニュケーションツールとしてのエクソソームの役割2018

    • Author(s)
      上原 範久, 久本 由香里, 久木田 明子, 久木田 敏夫
    • Organizer
      日本解剖学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Extracellular vesicles from bone metastatic mammary tumor cells facilitate osteoclast formation and bone resorption in vitro2017

    • Author(s)
      上原 範久, 久本 由香里, 久木田 明子, 久木田 敏夫
    • Organizer
      日本骨代謝学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Bone metastatic mammary tumor cell-derived extracellular vesicles as positive regulator of osteoclastogenesis2016

    • Author(s)
      上原 範久、久本由香里、久木田明子、久木田敏夫
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス骨転移性乳癌細胞由来エクソソームは破骨細胞分化を促進する2016

    • Author(s)
      上原 範久、久本由香里、久木田明子、久木田敏夫
    • Organizer
      日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] 分泌型miRNAを介した骨転移性癌細胞-破骨細胞間コミュニケーション2016

    • Author(s)
      上原 範久、久本 由香里、久木田 明子、久木田 敏夫
    • Organizer
      日本解剖学会
    • Place of Presentation
      福島
    • Year and Date
      2016-03-30
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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