| Project/Area Number |
18590048
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
MIYAURA Chisato Tokyo University of Agriculture and Technology, Institute of Symbiotic Science and Technology, Professor (20138382)
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| Co-Investigator(Kenkyū-buntansha) |
INADA Masaki Tokyo University of Agriculture and Technology, Institute of Symbiotic Science and Technology, Senior Assistant Professor (80401454)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Prostaglandin E / bone metastasis of cancer / Lung metastasis of cancer / solid tumor / Cancer / bone and mineral metabolism / 生化学 |
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| Research Abstract |
We examined bone metastasis, subcutaneous tumor formation and lung metastasis by the injection of mouse malignant melanoma B16 cells into prostaglandin E (PGE) synthase gene deficient mice. Furthermore, we analyzed the mechanism and effectivity of PGE receptor antagonist for these events. The detail is following below :
1. Experimental metastasis using membrane-bound PGE synthase (mPGES) deficient mice
We performed the experimental metastasis by the injection of mouse malignant melanoma B16 cells into mice. Bone and lung metastases was happened at high rate by the injection of B16 cells into tail vein of mice. We performed B16 experimental metastasis using mPGES deficient mice or wild-type mice. Femur and lung were collected on 14 days after B16 injection. Bone metastasis was analyzed by femur. Lung metastasis was analyzed by colony-counting in surface of lung and staining of histological section. As a result, both bone and lung metastases were markedly attenuated in mPGES deficient mice. When EP4 antagonist was orally administered to wild-type mice injected with B16 cells, lung metastases were also markedly attenuated.
2. Role of PGE2 in subcutaneous tumor formation
To form subcutaneous tumor, B16 cells were dorsal subcutaneous injected into mPGES deficient or wild-type mice. Tumor volume was measured by caliper every other day. As a result, tumor growth accompanied with angiogenesis was markedly attenuated in mPGES deficient mice. When EP4 antagonist was topically administered to wild-type mice injected with B16 cells, tumor growth was also markedly attenuated.
Therefore, we conclude that host cells-derived PGE2 is involved in metastasis and solid tumor formation of malignant melanoma cells, and promotes growth and metastasis of cancer via EP4 expressed in host cells. Some possible mechanisms of that are regulation of angiogenesis and tumor immunity.
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