tumor microenvironment in lung metastasis of sarcoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: Takenaka Satoshi 大阪大学, 医学系研究科, 助教 (00588379)
• Research Collaborator: Yasuda Naohiro ; Nakai Sho ; Mae Hirokazu ; Outani Hidetatsu ; Hamada Kenichiro ; Nakai Takaaki ; Yamada shutaro ; Imura Yoshinori ; Naka Norifumi ; Yoshikawa Hideki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 骨肉腫 / 肺転移 / チロシンキナーゼ

Outline of Final Research Achievements

AXL signaling was more activated in the lung metastasis than in primary tumor of LM8, mouse osteosarcoma cell line. TAS115, a multiple tyrosine kinase inhibitor, inhibited the proliferation in vitro, the growth of tumor implanted under the skin, and lung metastasis of the LM8, highly lung metastasis cell line of mouse osteosarcoma, by inhibition of phosphorylation of PDGFR, AXL, and Flt3. TAS115 also inhibited the proliferation of some other human osteosarcoma cell lines. We found that GAS6, a ligand of AXL, promoted the proliferation of LM8, but co-culture of LM8 with osteoblast, fibroblast, or MSC did not show proliferative effect of LM8 or secretagogue response of GAS6.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

現在、転移性骨肉腫に対して複数のMultiple tyrosine kinase inhibitorの臨床試験が進行中であり、本邦ではTAS115のPhase1試験が行われている。本研究ではマウス骨肉腫高肺転移株LM8やその他の骨肉腫細胞株を用いて、TAS115の有効性を示し、肺転移の増大抑制効果も示した。また、肺転移巣増大を抑制する新たな治療標的分子としてAXLを見出したが、今後のさらなる検討が必要と考える。