MP46-16 CASTRATION-INDUCED ACCELERATION OF BONE METASTASIS PREVENTED BY RANK INHIBITOR OSTEOPROTEGERIN IN MURINE CASTRATION-RESISTANT PROSTATE CANCER MODEL

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2015MP46-16 CASTRATION-INDUCED ACCELERATION OF BONE METASTASIS PREVENTED BY RANK INHIBITOR OSTEOPROTEGERIN IN MURINE CASTRATION-RESISTANT PROSTATE CANCER MODEL Koichiro Takayama, Takamitsu Inoue, Shintaro Narita, Mingguo Huang, Yoko Mitobe, Hiroshi Tsuruta, Susumu Akihama, Mitsuru Saito, Norihiko Tsuchiya, and Tomonori Habuchi Koichiro TakayamaKoichiro Takayama More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Yoko MitobeYoko Mitobe More articles by this author , Hiroshi TsurutaHiroshi Tsuruta More articles by this author , Susumu AkihamaSusumu Akihama More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1579AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen deprivation therapy (ADT) decreases bone mineral density by stimulating RANK signaling in osteoclasts. It has been reported that the RANK inhibitor osteoprotegerin (OPG) prevents bone metastases in a murine prostate cancer model. However, the possibility of castration-induced acceleration of bone metastasis in castration-resistant prostate cancer (CRPC) has not been examined. Here, the effect of castration on bone mineral density and bone metastases was investigated using a murine CRPC model. METHODS Male Balb/c nude mice were divided into three groups: the noncastration group, the castration group, and the castration + OPG group. OPG was intravenously injected (2 mg/kg) twice a week in the castration + OPG group. A human CRPC cell line (PC3M–luc–C6), which is prone to the formation of bone metastases and has luciferase activity, was injected into the left ventricle of mice. Bone mineral density was measured by microcomputed tomography twice a week. Three weeks after injection into the ventricle, the number of mice with bone metastasis, the mean number of bone metastases, and mean photon counts of bone metastases were measured using the IVIS imaging system§ (Xenogen, Alameda, CA, USA). RESULTS Two weeks after castration, bone mineral density in the castration group was significantly lower than that in the noncastration group and the castration + OPG group (p = 0.034 and p = 0.010, respectively). The number of mice with bone metastases in the castration group was significantly higher than that in the noncastration group and the castration + OPG group (p = 0.024 and p = 0.028, respectively). The mean number of bone metastases and the mean photon counts of bone metastases in the castration group was significantly higher than those in the castration + OPG group (p = 0.020 and p = 0.041, respectively). CONCLUSIONS Castration reduced bone mineral density and accelerated bone metastasis in the murine CRPC model. OPG prevented both bone mineral loss and bone metastasis. The castration-induced acceleration of bone metastasis in CRPC could be caused by activation of osteoclasts due to RANK signaling. These results suggested that it is necessary to inhibit RANK signaling from the beginning of ADT to prevent bone metastasis in prostate cancer patients. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e549-e550 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Koichiro Takayama More articles by this author Takamitsu Inoue More articles by this author Shintaro Narita More articles by this author Mingguo Huang More articles by this author Yoko Mitobe More articles by this author Hiroshi Tsuruta More articles by this author Susumu Akihama More articles by this author Mitsuru Saito More articles by this author Norihiko Tsuchiya More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...