| Project/Area Number |
26460445
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
秋山 隆 川崎医科大学, 医学部, 准教授 (80294411)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 血管肉腫 / Sphingosine-1-phosphate / S1PR1 / FTY720 / 細胞運動 / 転移 / 免疫組織化学 / sphingosine-1-phosphate / STAT3 / sphingosine kinase 1 / VCAM-1 / スフィンゴシン-1-リン酸レセプター1 / スフィンゴシン－1－リン酸レセプター１ / 細胞走化性 / 細胞遊走 / siRNA |
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| Outline of Final Research Achievements |
We investigated the effect of S1PR1 modulation on cell migration, and examined its potential role as a therapeutic target against metastatic dissemination of angiosarcoma. Immunostaining revealed high expression of S1PR1 on a angiosarcoma cell line MO-LAS cell membrane. S1P enhanced chemotactic and random migration of MO-LAS cells, respectively. Inhibition of S1PR1 expression with siRNA significantly attenuated chemotaxis of cells towards S1P. Further, FTY720P strongly induced the internalization and degradation of S1PR1 even in the presence of serum containing S1P. It attenuated chemotactic cell migration of MO-LAS towards both S1P and serum, as well as the random motility of cells at nanomolar concentrations. We found that all angiosarcoma cases showed high expression of S1PR1, sphingosine kinase 1, and phospho-STAT3. Thus, SK1/S1P/S1PR1/STA3 axis may be a potential therapeutic target for inhibition of angiosarcoma metastasis by controlling its cell motility.
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