2016 Fiscal Year Final Research Report
Sphingosine-1-phosphate receptor 1 as a potential therapeutic target for patients with angiosarcoma
| 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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| Project Period (FY) |
2014-04-01 – 2017-03-31
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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 |
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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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| Free Research Field |
病理学
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