title: Roles of microsomal prostaglandin E synthase-1 in lung metastasis formation in prostate cancer RM9 cells.
abstract: Cyclooxygenase-2 (COX-2) is known to correlate with a poor prognosis of prostate cancer and contribute to tumor metastasis. However, the precise mechanism of this phenomenon remains unknown. We have previously reported that host stromal microsomal prostaglandin E synthase-1 (mPGES-1) appeared critical for tumor-associated angiogenesis and tumor growth. Here, we tested whether or not mPGES-1 has a critical role in lung metastasis formation of prostate cancer. Murine prostate cancer cells (RM9) were intravenously injected and lung metastasis was estimated by counting colonies in the lungs. Mice treated with a selective COX-2 inhibitor, celocoxib, were suppressed lung metastasis compared to vehicle mice. This lung metastasis formation was also reduced in mPGES-1 knockout (mPGES-1 KO) mice, compared with wild type (WT) mice. This was accompanied with reduced angiogenesis around the metastasized colonies of RM9. Plasma protein levels and metastasized lung tissue mRNA levels of vascular endothelial growth factor (VEGF) and stromal cell derived factor-1 (SDF-1) were significantly suppressed in mPGES-1 KO mice in comparison with WT mice. In addition, the expressions of matrix metalloproteinases (MMP)-9, and metalloproteinases (MMP)-2 were down-regulated in metastatic lungs in mPGES-1 KO mice. These results suggested that host mPGES-1 was essential for MMP-2 and MMP-9 up-regulation that enhances tumor metastasis. mPGES-1 appears to be critical for tumor metastasis in prostate cancers. mPGES-1 inhibitors may be useful to protect against prostate cancer metastasis.
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan; Department of Urology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Amano
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tabata
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Microbiology, Kitasato University School of Allied Health Science, Kanagawa 252-0373, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kitasato
authors.affiliation: Laboratory of Host Defense, Osaka University, Osaka 565-0871, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Akira
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iwamura
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan. Electronic address: mmajima@med.kitasato-u.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Majima
mesh_terms: D000818:Animals; D000068579:Celecoxib; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008175:Lung Neoplasms / Q000473:pathology* / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008861:Microsomes / Q000201:enzymology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D000071876:Prostaglandin-E Synthases; D011471:Prostatic Neoplasms / Q000473:pathology*; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D000068579:Celecoxib
keywords: COX-2; Matrix metalloproteinases; Metastasis; Prostate cancer; mPGES-1