Involvement and function elucidation of stromal cells in the process of bone invasion of odontogenic tumors

• Project/Area Number: 17K11865
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Okayama University of Science
• Principal Investigator: Tsujigiwa Hidetsugu 岡山理科大学, 理学部, 教授 (70335628)
• Co-Investigator(Kenkyū-buntansha): 山近 英樹 岡山大学, 大学病院, 講師 (10294422) ; 長塚 仁 岡山大学, 医歯薬学総合研究科, 教授 (70237535)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 歯原性腫瘍 / 骨浸潤 / 腫瘍間質相互作用 / エクソソーム / 微小環境

Outline of Final Research Achievements

Various studies have been conducted on ameloblastoma, however the details of their bone invasion mechanism remain unclear. In this study, we investigated the effects of tumor-stromal interactions in bone invasion of ameloblastoma. In ameloblastoma, tumor cells were thought to produce factors that suppress osteoblast differentiation. And also in ameloblastoma, it was considered that the stromal fibroblasts derived from tumor tissue was activated by tumor cells and promote to product MMPs , thus the stromal fibroblasts acquire the invasion bone ability. These results suggested that in ameloblastoma, bone invasion may be promoted by tumor-specific tumor-stromal interaction.

Academic Significance and Societal Importance of the Research Achievements

本研究により、エナメル上皮腫では腫瘍特異的な腫瘍間質細胞の相互作用により、骨芽細胞の分化抑制が生じ、骨組織の新生を阻害するとともに、間質線維芽細胞が腫瘍周囲組織に作用することで腫瘍細胞の浸潤を促進させている可能性が考えられた。
これらの研究成果は、エナメル上皮腫および、扁平上皮癌等エナメル上皮腫以外の腫瘍浸潤メカニズム解明に貢献すると考えられる。また、今後エナメル上皮腫の新規治療法開発に向けた基礎研究の発展に寄与することが考えられる。

Research Products

• [Journal Article] Impact of the Stroma on the Biological Characteristics of the Parenchyma in Oral Squamous Cell Carcinoma (2020)
  • Author(s): Takabatake Kiyofumi、Kawai Hotaka、Omori Haruka、Qiusheng Shan、Oo May Wathone、Sukegawa Shintaro、Nakano Keisuke、Tsujigiwa Hidetsugu、Nagatsuka Hitoshi
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 20 Pages: 7714-7714
  • DOI: 10.3390/ijms21207714
  • NAID: 120006900773
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma (2019)
  • Author(s): Takabatake K, Shimo T, Murakami J, Anqi C, Kawai H, Yoshida S, Wathone Oo M, Haruka O, Sukegawa S, Tsujigiwa H, Nakano K, Nagatsuka H.
  • Journal Title: Int J Mol Sci Volume: 20(22) Issue: 22 Pages: 5779-5779
  • DOI: 10.3390/ijms20225779
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differentiation and roles of bone marrow-derived cells on the tumor microenvironment of oral squamous cell carcinoma (2019)
  • Author(s): Anqi C, Takabatake K, Kawai H, Oo MW, Yoshida S, Fujii M, Omori H, Sukegawa S, Nakano K, Tsujigiwa H, Jinhua Z, Nagatsuka H.
  • Journal Title: Oncol Lett Volume: 18(6) Pages: 6628-6638
  • DOI: 10.3892/ol.2019.11045
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] エナメル上皮腫および間質との相互作用が骨組織におよぼす影響について (2018)
  • Author(s): 澄 文香、阪上峻基、浜田芽衣、高畠清文、長塚 仁、辻極秀次
  • Organizer: 第27回硬組織再生生物学会学術大会・総会
• [Presentation] エナメル上皮腫および腫瘍間質線維芽細胞におよぼす影響について (2018)
  • Author(s): 阪上 峻基、澄 文香、浜田 芽衣、長塚 仁、辻極 秀次
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] エナメル上皮腫細胞と骨芽細胞の細胞間相互作用解析 (2017)
  • Author(s): 澄 文香, 阪上峻基, 浜田芽衣, 長塚 仁, 辻極秀次
  • Organizer: 日本組織培養学会 第90回大会