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Development of a novel mouse model that recapitulates bone metastasis seen in human.

Research Project

Project/Area Number 26670806
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

Yoneda Toshiyuki  大阪大学, 歯学研究科(研究院), 招へい教員 (80142313)

Co-Investigator(Renkei-kenkyūsha) HATA Kenji  大阪大学, 大学院歯学研究科, 准教授 (80444496)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords骨転移 / 動物モデル / 遺伝子改変マウス / 動物実験モデル
Outline of Final Research Achievements

Many types of cancers preferentially spread to bone, developing bone metastases. To develop novel therapeutic interventions for bone metastasis and to test their effectiveness, establishment of pre-clinical animal models that resemble bone metastasis occurring in cancer patients has been awaited. Here, we attempted to develop a novel mouse model that recapitulates the entire steps of bone metastasis seen in human. The MMTV-Cdh11-2A-ffLuc transgenic (Tg) vectors were designed and constructed. The ffLuc is a novel chemiluminescent/fluorescent protein that enables the dynamic imaging of bone metastasis with high resolution. The linealized Tg vectors were then injected into fertilized eggs of FVB mice. Our next plan will be to generate double Tg mice by crossing MMTV-neu mice and MMTV-Cdh11-2A-ffLuc mice and monitor bone metastases spontaneously developed in these mice by in vivo imaging. This mouse model will be a useful tool to understand the mechanism underlying cancer bone metastasis.

Report

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

    (17 results)

All 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Int'l Joint Research] インディアナ大学(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Contribution of acidic extracellular microenvironment to cancer-associated bone pain2015

    • Author(s)
      Yoneda T, Hiasa M, Nagata Y, Okui T, White F
    • Journal Title

      Biochim Biophys Acta

      Volume: 印刷中 Issue: 10 Pages: 2677-2684

    • DOI

      10.1016/j.bbamem.2015.02.004

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acidic microenvironment and bone pain in cancer-colonized bone.2015

    • Author(s)
      Yoneda T, Hiasa M, Nagata Y, Okui T, White F
    • Journal Title

      BoneKey

      Volume: 4 Pages: 690-690

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] がんと骨微小環境2015

    • Author(s)
      米田俊之
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 64(2) Pages: 133-138

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma.2015

    • Author(s)
      Hiasa M, Teramachi J, Oda A, Amachi R, Harada T, Nakamura S, Miki H, Fujii S, Kagawa K, Watanabe K, Endo I, Kuroda Y, Yoneda T, Tsuji D et al.
    • Journal Title

      Leukemia

      Volume: 29 Issue: 1 Pages: 207-217

    • DOI

      10.1038/leu.2014.147

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cyclooxygenase-2 expression is associated with vascular endothelial growth factor-c and lymph node metastasis in human oral tongue cancer2014

    • Author(s)
      Morita Y, Morita N, Hata K, Nakanishi M, Kimoto N, Omata T, Nakamura Y, Yoneda T
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol

      Volume: 117(4) Issue: 4 Pages: 502-510

    • DOI

      10.1016/j.oooo.2013.12.410

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone metastases of breast cancer2014

    • Author(s)
      Hata K, Yoneda T
    • Journal Title

      Clin Calcium

      Volume: 24 Pages: 1177-1184

    • Related Report
      2014 Research-status Report
  • [Journal Article] The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression.2014

    • Author(s)
      Tsutsumimoto T, Williams P, Yoneda T
    • Journal Title

      J Bone Oncol

      Volume: 3 Issue: 3-4 Pages: 67-76

    • DOI

      10.1016/j.jbo.2014.10.002

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Osteocytes are an Important Mediator of Bone Pain in Myeloma2015

    • Author(s)
      Hiasa M, Okui T Nagata Y, Allette YM, Ripsch MS, Delgado-Calle J, Bellido T, Roodman DG, Plotkin R, White F, Yoneda T
    • Organizer
      ASBMR annual meeting
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Reciprocal Interactions between Sensory Neurons and Tumor Cells Promote Breast Cancer Progression in Bone, Secondary Visceral Metastasis and Bone Pain2015

    • Author(s)
      Okui T, Hiasa M, Nagata Y, White F, Roodman DG,Yoneda T
    • Organizer
      ASBMR annual meeting
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Contribution of osteocytes to cancer-associated bone pain via connexin43-mediated communications with sensory neurons under the acidic microenvironment in bone metastasis2015

    • Author(s)
      Yoneda T, Hiasa M, Okui T, Ripsch MS, Delgado-Calle J, Bellido T, Roodman DG, Plotkin R, White F
    • Organizer
      4th joint meeting of ECTS and IBMS
    • Place of Presentation
      Rotterdam, The Netherlands
    • Year and Date
      2015-04-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Acidic extracellular microenvironment in myeloma-colonized bone contributes to bone pain.2014

    • Author(s)
      Yoneda T, Hiasa M, Nagata Y, Ripsch MS, White FA
    • Organizer
      Annual Meeting of the American Society of Hematology,
    • Place of Presentation
      San Francisco
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 骨痛誘発における骨転移巣の酸性環境の貢献.2014

    • Author(s)
      米田俊之
    • Organizer
      岡山骨生物学セミナー
    • Place of Presentation
      岡山
    • Year and Date
      2014-11-19
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Acidic microenvironment contributes to the pathophysiology of bone pain associated with cancer colonization.2014

    • Author(s)
      Yoneda T
    • Organizer
      7th International Conference on Osteoporosis and Bone Research/ International Bone and Mineral Society joint symposium
    • Place of Presentation
      Xiamen
    • Year and Date
      2014-10-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Osteocytes directly communicate with sensory neuronal cells in bone via cell-cell networks that are modulated under an acidic microenvironment.2014

    • Author(s)
      Hiasa M, Nagata Y, Delgado-Calle J, Allette Y, Ripsch MS, Bellido T, Roodman GD, White FA, Yoneda T.
    • Organizer
      Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Houston
    • Year and Date
      2014-09-12 – 2014-09-15
    • Related Report
      2014 Research-status Report
  • [Presentation] Ubiquitin-specific peptidase 45 (USP45), a family member of de-ubiquitinating enzyme, controls epithelial-mesenchymal transition of breast cancer in bone.2014

    • Author(s)
      Nagata Y, Tanaka S, Hata K, Hiasa M, Nishimura R, Yoneda T.
    • Organizer
      Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Houston
    • Year and Date
      2014-09-12 – 2014-09-15
    • Related Report
      2014 Research-status Report
  • [Presentation] Bone metastasis: Integrated achievements by characteristic players2014

    • Author(s)
      米田俊之
    • Organizer
      第32回日本骨代謝学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-24
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2017-05-10  

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