| Project/Area Number |
25860192
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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 |
General pharmacology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | リンパ管新生 / プロスタグランジン / リンパ節転移 / がん / 慢性炎症 / ノックアウトマウス |
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| Outline of Final Research Achievements |
Lymph node metastasis (LNM) is a critical prognostic factor in cancer patients. Our study revealed that endogenous COX-2-derived PGE2 stimulated the EP3 receptor on DCs, leading to theupregulation of SDF-1 expression in the subcapsular regions in regional lymph nodes following LLC cell injection into the lungs. SDF-1 upregulation facilitated the accumulation of CXCR4+ LLC cells and the formation of the regional lymph node premetastatic niche. We also found that accumulation of Tregs and lymph node lymphangiogenesis, both of which may decide the fate of metastasized tumor cells, were COX-2/EP3-dependent. Taken together, our findings suggest that PGE2inhibitors, together with SDF-1 receptor antagonists and EP3 antagonists, may be promising agents for the suppression of premetastatic niche formation and LNM.
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