Functional analysis of circulating tumor cells and epithelial-mesenchymal transition and inhibition of lung metastasis in osteosarcoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16679
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: University of Fukui (2020); Osaka International Cancer Institute (2018-2019)
• Principal Investigator: Tanaka Takaaki 福井大学, 学術研究院医学系部門, 講師 (00796245)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 骨肉腫 / 血中循環腫瘍細胞 / 上皮間葉移行 / 肺転移

Outline of Final Research Achievements

The mouse osteosarcoma high lung metastasis strain LM8 and its parental strain Dunn were used. (1) LM8 was implanted subcutaneously in mice, and live CTCs were collected by direct floating culture of blood. The RNA was extracted from LM8 in 2D culture and LM8-CTC in 3D culture, and the difference in RNA was analyzed. (2) LM8 and Dunn were cultured in 2D culture, and the cell supernatant was collected for exosome analysis. (1) No difference in RNA between LM8 and LM8-CTC was observed. This may be due to the fact that CTCs consist of several to dozens of clusters, and the subtle differences in expression were eliminated by floating culture. However, in (2), we found a large difference in metastasis-related factor A between LM8 and Dunn.

Free Research Field

整形外科学関連

Academic Significance and Societal Importance of the Research Achievements

骨肉腫は年間発生が約200例と非常に稀であり、若年齢層に好発する骨悪性腫瘍である。手術、化学療法、放射線治療を含めた集学的治療により5年生存率は8割程度であるが、肺転移例では2割程度と予後不良である。このため、骨肉腫治療においては原発巣のコントロールだけでなく、転移抑制を目的とした治療法が渇望されている。近年、転移形成において血中循環腫瘍細胞(CTC)の存在が重要な役割を果たすとの報告が多くされており、その機能を解析することは骨肉腫患者の予後改善につながることから意義のある研究である。