Elucidation of the mechanisms for bone destruction in chordoma.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18401
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Keio University
• Principal Investigator: SATO Mizuto 慶應義塾大学, 医学部(信濃町), 助教 (70836759)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脊索腫 / 骨破壊 / 破骨細胞 / 骨芽細胞 / リモデリング

Outline of Final Research Achievements

Although chordomas tend to grow slowly, patients develop severe symptoms such as cranial nerve palsies and brain stem compression, that make successful surgical treatment difficult, and become resistant to radiochemotherapy. In the present study, mico-CT scanning demonstrated that bone density was lower in the clivus with invaded chordoma, suggesting acidic microenvironment in chordoma. Histopathological analysis revealed that Cathepsin K and MMP-13 were expressed in chordoma cells. The expression of MMP-13 may be associated with the poor clinical course of the patients with chordoma. However, it was difficult to establish chordoma mouse model, because the growth speed of chordoma cells implanted into the calvaria and sacrum was slow. in vitro and in vivo analyses using human chordoma cells are indispensable. Further analyses should be conducted using human chordoma cells to evaluate tumor biology, including bone destruction.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

脊索腫は斜台や仙骨に生じる骨破壊性の腫瘍であり、あらゆる集学的治療を行っても根治することは困難な難治性疾患である。骨破壊によって生じる脳神経麻痺が患者の日常生活動作に大きく影響するため、骨破壊の機序を解明することは新規治療の開発には必須である。本研究では脊索腫腫瘍細胞がタンパク分解酵素を発現していること、およびヒト脊索腫細胞株の担空胞細胞内に多数の酸性顆粒の存在が確認された。以上のことから、腫瘍細胞自体が酸とタンパク分解酵素を分泌し、骨破壊に関与している可能性が示唆された。今後、さらに症例数を蓄積し、骨破壊に直接的に寄与する機序を同定し、これらをターゲットとした新たな治療法の開発につなげたい。