| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Research Abstract |
Prostate cancer is the most commonly malignancy in elderly men in Japan. We have previously reported that host stromal microsomal prostaglandin E synthase-1 (mPGES-1) signaling appeared critical for tumor-associated angiogenesis and tumor growth. We estimated whether mPGES-1 has a critical role in prostate cancer in lung metastasis formation or not.Murine prostate cancer cells (RM9) were intravenously injected to Wild type mice (WT) and mPGES-1 knockout mice (mPGES-1 KO). Lung metastasis was estimated by counting colonies in the lung and the lung weight. Angiogenesis was estimated by measuring plasma level and mRNA expression of angiogenesis stimulates factors, VEGF-A and SDF-1, and microvessel density and microvessel area in the lung.The lung metastasis formation was significantly suppressed in mPGES-1 KO mice compared with WT mice.The number of colonies and the weight of lung is significantly reduced in mPGES-1 KO mice.The plasma and mRNA level of vascular endothelial growth factor (VEGF) and stromal derived factor-1 (SDF-1) were significantly suppressed in mPGES-1 KO mice.The plasma levels of SDF-1 in mPGES-1KO mice were decreased compared with WT.The expressions of VEGF-A and SDF-1 in the lung tissue were significantly suppressed in mPGES-1KO mice. We thought that mPGES-1was important in RM9 hematogenous metastasis to the lungs and in the colonization of tumors after extravasation.The present results indicated that the selective mPGES-1 inhibitors under development will be a promising therapeutic tool for the inhibition of tumor hematogenous metastasis.
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