| Project/Area Number |
16K20050
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
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| Research Collaborator |
Yasuda Naohiro
Nakai Sho
Mae Hirokazu
Outani Hidetatsu
Hamada Kenichiro
Nakai Takaaki
Yamada shutaro
Imura Yoshinori
Naka Norifumi
Yoshikawa Hideki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 骨肉腫 / 肺転移 / チロシンキナーゼ / LM8 / 微小環境 / 肉腫 / 間葉系幹細胞 / 腫瘍微小環境 / 癌 |
|---|
| 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.
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| 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。
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