Diversity of cancer-mediated bone destruction in oral squamous carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K23024
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Osaka 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
• Keywords: 口腔扁平上皮癌 / 骨破壊 / 破骨細胞

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.

Free Research Field

口腔外科学

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。