PT - JOURNAL ARTICLE AU - Ryo Takahashi AU - Hideki Amano AU - Masataka Majima TI - Roles of microsomal prostaglandin E synthase-1 in lung metastasis formation in prostate cancer cells in mice DP - 2014 Sep 01 TA - European Respiratory Journal PG - P2707 VI - 44 IP - Suppl 58 4099 - http://erj.ersjournals.com/content/44/Suppl_58/P2707.short 4100 - http://erj.ersjournals.com/content/44/Suppl_58/P2707.full SO - Eur Respir J2014 Sep 01; 44 AB - <Background>We have previously reported that host stromal microsomal prostaglandin E synthase-1 (mPGES-1) signaling appeared critical for tumor-associated angiogenesis and tumor growth. Here, we estimated whether mPGES-1 has a critical role in prostate cancer in lung metastasis formation or not.<Material and methods>Murine prostate cancer cells (RM9) were intravenously injected to Wild type mice (WT) and mPGES-1 knockout mice (mPGES-1KO). Lung metastasis was estimated by number of colonies in the lung and the lung weight. Angiogenesis was estimated by measuring plasma level and mRNA expression of VEGF-A and SDF-1, and microvessel density and microvessel area in the lung.<Results>Lung metastasis formation was significantly suppressed in mPGES-1 KO mice compared with WT mice. The plasma levels of VEGF-A in mPGES-1 KO mice on day 21 after injection of the prostate cancer cells were found to be lower than that in WT (WT:4.83±0.51pg/ml, mPGES-1 KO:3.29±0.21pg/ml, P<0.05). In addition, the plasma levels of SDF-1 in mPGES-1KO mice were decreased compared with WT (WT:1.51±0.43ng/ml, mPGES-1 KO:0.45±0.13ng/ml, P<0.05).The expressions of VEGF-A and SDF-1 in the lung tissue were significantly suppressed in mPGES-1KO mice.Furthermore, the expressions matrix metalloproteinases (MMP)-9, metalloproteinases (MMP)-2 were down-regulated in metastatic lungs of mPGES-1 KO mice.<Conclusions>These results suggested that mPGES-1 signaling in stroma was essential for MMP-2 and MMP-9 up-regulation that enhances angiogenesis and tumor metastasis. The selective mPGES-1 inhibitors under development will be a promising therapeutic tool for the inhibition of tumor hematogenous metastasis.