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Diversity of cancer-mediated bone destruction in oral squamous carcinoma

Research Project

Project/Area Number 20K23024
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0907:Oral science and related fields
Research InstitutionOsaka University

Principal Investigator

Miyagawa Kazuaki  大阪大学, 歯学部附属病院, 医員 (50635381)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords口腔扁平上皮癌 / 骨破壊 / 破骨細胞 / 口腔癌 / がんの骨病変 / 口腔がん / 癌ー間質相互作用 / 癌-間質相互作用 / 骨吸収 / IL-6
Outline of Research at the Start

歯肉に発生するがん(扁平上皮癌)は歯肉癌とよばれ、癌細胞は癌組織内やその周辺に骨吸収を生じさせる破骨細胞を誘導し、顎骨を破壊させながら深部へと進展する。この骨破壊には積極的に骨破壊する浸潤型と骨破壊が緩慢な圧排型に分類され、治療計画を決めるうえで重要な特徴である。しかしながら、この骨破壊の違いがどうして発生するのかという科学的根拠はいまだ不明である。本研究は、歯肉癌の骨破壊は癌細胞の性質が破骨細胞の活性化に違いをもたらすと考え、癌細胞から分泌されるIL-6の量と破骨細胞の性質がどのように変化するのかについて、2種類の歯肉癌マウスモデルを作成・比較することで明らかにしてゆく。

Outline of Final Research Achievements

Bone invasions by oral squamous cell carcinoma (OSCC) are classified into two types: one is the invasion type which abnormal activation of osteoclasts causes bone resorption, and the other is the compressive type which is slowly progressive bone resorption. In this study, we investigated the molecular mechanisms that determine the bone resorption phenotypes by OSCC using syngeneic mouse models of OSCC. Syngeneic carcinoma-bearing mouse models in which tumors (destructive and compressive types) were formed were generated due to seed two subtypes of a murine squamous cell carcinoma cell line near parietal periosteum in calvaria of C3H mice. These were compared to bone phenotypes. The results showed that factor X, which is involved in cellular immunity, was higher gene expression in the invasive type than in the compressed type. This study suggested that tumor cells expressing high levels of factor X may promote bone resorption dependent on T lymphocytes in the tumor tissue.

Academic Significance and Societal Importance of the Research Achievements

我が国における口腔がんの患者数は近年急増している。歯肉癌と呼ばれる口腔扁平上皮癌の顎骨浸潤には浸潤型と圧迫型に大別され、治療法の選択や予後の予測に重要である。本研究は骨破壊の表現型によって腫瘍内に起きている状況を探索した結果、破骨細胞形成に関わる免疫機構に違いがあることを見出した。この結果は顎骨浸潤を伴う口腔扁平上皮癌の新規治療や予後を予測するための検査に応用することができる可能性を含んでいる。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2021 2020

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

  • [Journal Article] Comparative evaluation of bone microstructure in alveolar cleft repair by cone beam CT: influence of different autologous donor sites and additional application of <i>β </i>-tricalcium phosphate2020

    • Author(s)
      MIYAGAWA Kazuaki、TANAKA Susumu、HIROISHI Sachie、MATSUSHITA Yutaka、KOGO Mikihiko
    • Journal Title

      Japanese Journal of Oral and Maxillofacial Surgery

      Volume: 66 Issue: 12 Pages: 660-668

    • DOI

      10.5794/jjoms.66.660

    • NAID

      130007989814

    • ISSN
      0021-5163, 2186-1579
    • Year and Date
      2020-12-20
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased S1P expression in osteoclasts enhances bone formation in an animal model of Paget's disease2020

    • Author(s)
      Nagata Yuki、Miyagawa Kazuaki、Ohata Yasuhisa、Petrusca Daniela N.、Pagnotti Gabriel M.、Mohammad Khalid S.、Guise Theresa A.、Windle Jolene J.、David Roodman G.、Kurihara Noriyoshi
    • Journal Title

      Journal of Cellular Biochemistry

      Volume: 122 Issue: 3-4 Pages: 335-348

    • DOI

      10.1002/jcb.29861

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Osteoclast-derived IGF1 alters osteocyte function and is an important contributor to the development of Paget’s disease.2021

    • Author(s)
      Miyagawa K, Mulcrone PL, Delgado-Calle J, Subler M, Windle JJ, Chirgwin JM, Roodman GD, Kurihara N.
    • Organizer
      The American Society for bone and mineral research 2021 Annual Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アメリカ留学報告 ーインディアナ大学での研究生活ー2020

    • Author(s)
      宮川和晃
    • Organizer
      第65回日本口腔外科学会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-09-29   Modified: 2023-01-30  

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