Lung fibrosis is a novel therapeutic target to suppress lung metastasis of osteosarcoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16641
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: 医療法人徳洲会野崎徳洲会病院(附属研究所)
• Principal Investigator: Yui Yoshihiro 医療法人徳洲会野崎徳洲会病院(附属研究所), 研究所, 主任研究員 (20547757)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 骨肉腫 / 転移 / 線維化抑制剤

Outline of Final Research Achievements

The prognosis of patients with osteosarcoma has not improved over the last 30 years. In this study, we examined the metastasis-promoting effect of lung fibrosis in metastatic lesions and its potential as a therapeutic target in lung metastasis of osteosarcoma. We confirmed that lung fibrosis with activated fibroblasts progressed with the lung metastasis of osteosarcoma and that lung fibrosis in a bleomycin model promoted lung metastasis of osteosarcoma. The proliferation of osteosarcoma cells was dependent on the amount of collagen fiber on soft polyacrylamide gels. Anti-fibrotic agents significantly suppressed lung metastasis in a mouse model of osteosarcoma lung metastasis. Anti-fibrotic agents may effectively suppress lung metastasis of osteosarcoma, which has low adaptability to soft environments.

Free Research Field

がん転移

Academic Significance and Societal Importance of the Research Achievements

骨肉腫の予後は、肺転移に対して有効な治療法が開発されずに30年間大きな改善がない。様々な分子標的薬が試みられてきたが、肺転移抑制に有用性を示すものは見つかっていない。本研究は、腫瘍外環境の一要因である腫瘍周囲の線維化を治療標的とすることで、骨肉腫の肺転移を抑制できる可能性を示したものである。肺線維化抑制は、骨肉腫の新規治療戦略として今後臨床応用につながる可能性がある。