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Induction of disruption of tumor parenchymal-stromal interactions by controlling the biological characteristics of ameloblastoma

Research Project

Project/Area Number 20K10094
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionOkayama University

Principal Investigator

Fujii Masae  岡山大学, 歯学部, 博士研究員 (30362685)

Co-Investigator(Kenkyū-buntansha) 長塚 仁  岡山大学, 医歯薬学域, 教授 (70237535)
中野 敬介  岡山大学, 医歯薬学域, 准教授 (10325095)
高畠 清文  岡山大学, 医歯薬学域, 助教 (70736537)
河合 穂高  岡山大学, 医歯薬学域, 助教 (10803687)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Discontinued (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsエナメル上皮腫 / 腫瘍実質 / 腫瘍間質 / 開窓術 / 細胞競合 / 腫瘍微小環境 / 腫瘍実質間質相互作用 / 腫瘍実質-間質相互作用
Outline of Research at the Start

申請者らは歯原性腫瘍の腫瘍実質と腫瘍間質の相互作用に着目した研究を行い、その結果、腫瘍間質には未分化で骨芽細胞に分化しうる細胞が存在することを発見している。この未分化な細胞に対して腫瘍実質が産生する因子が分化抑制を行い、細胞浸潤や骨吸収に影響を与える研究成果を得ている。さらに、開窓術によりエナメル上皮腫が正常口腔粘膜上皮と連続することで、腫瘍実質が抑制的に制御されるとの研究成果を得ている。
本申請課題では、正常粘膜上皮との連続による腫瘍実質の生物学的性格の変化を利用し、腫瘍実質と腫瘍間質の相互作用機構を破綻させ、外科的手法を用いないエナメル上皮腫の新規治療法の開発に向けた基礎的研究を行う。

Outline of Final Research Achievements

In this project, we conducted basic research to establish a novel non-surgical treatment for ameloblastoma by disrupting the interaction between the tumor parenchyma and tumor stroma and shrinking the tumor, based on the fact that the biological characteristics of the tumor parenchyma change when it is contiguous with the normal mucosal epithelium.
In marsupialization, in which ameloblastoma is contiguous with normal mucosal epithelium, the histologic characteristics of ameloblastoma underwent squamous metaplasia, and the tumor stroma changed from a fibrous to an edematous myxoid appearance. Hypoxia inducible factor-1α, which has been reported to be involved in tumor growth, was downregulated before and after marsupialization for ameloblsatoma.

Academic Significance and Societal Importance of the Research Achievements

エナメル上皮腫は,20~30歳代の若年者に発症し、発育緩慢な良性腫瘍でありながら局所浸潤性、特に高い骨浸潤性を有する特徴があり準悪性腫瘍として扱われる。エナメル上皮腫の治療に関しては、開窓術をはじめとする顎骨保存療法や顎骨切除術が選択される。しかし、外科的処置後の患者のQOLは著しく低下し、審美性も大きく低下する。そのため、本申請課題の成果により導かれた、エナメル上皮腫の外科的手法を用いない新規治療法開発に向けた基礎的研究の成果は、口腔外科領域に対する貢献度は多大と考えられる。

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2022 2020

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

  • [Journal Article] SOD3 Expression in Tumor Stroma Provides the Tumor Vessel Maturity in Oral Squamous Cell Carcinoma2022

    • Author(s)
      Oo May Wathone、Kawai Hotaka、Eain Htoo Shwe、Soe Yamin、Takabatake Kiyofumi、Sanou Sho、Shan Qiusheng、Inada Yasunori、Fujii Masae、Fukuhara Yoko、Wang Ziyi、Sukegawa Shintaro、Ono Mitsuaki、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 11 Pages: 2729-2729

    • DOI

      10.3390/biomedicines10112729

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line derived xenograft model2022

    • Author(s)
      Shan Qiusheng、Takabatake Kiyofumi、Omori Haruka、Kawai Hotaka、Oo May、Sukegawa Shintaro、Fujii Masae、Inada Yasunori、Sano Sho、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Oncology Letters

      Volume: 24 Issue: 5 Pages: 382-382

    • DOI

      10.3892/ol.2022.13502

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Crosstalk between cancer and different cancer stroma subtypes promotes the infiltration of tumor associated macrophages into the tumor microenvironment of oral squamous cell carcinoma2022

    • Author(s)
      Shan Qiusheng、Takabatake Kiyofumi、Kawai Hotaka、Oo May、Sukegawa Shintaro、Fujii Masae、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      International Journal of Oncology

      Volume: 60 Issue: 6 Pages: 1-10

    • DOI

      10.3892/ijo.2022.5368

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 口腔扁平上皮癌におけるCXCR4の腫瘍血管での役割2020

    • Author(s)
      大森悠加、河合穂高、吉田沙織、藤井昌江、単秋生、高畠清文、中野敬介、長塚仁
    • Organizer
      第31回日本臨床口腔病理学会学術大会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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