Inhibition of the RANK/RANKL signaling with osteoprotegerin prevents castration-induced acceleration of bone metastasis in castration-insensitive prostate cancer. (1st July 2017)

• Record Type: Journal Article
• Authors: Takayama, Koichiro; Inoue, Takamitsu; Narita, Shintaro; Maita, Shinya; Huang, Mingguo; Numakura, Kazuyuki; Tsuruta, Hiroshi; Saito, Mitsuru; Maeno, Atsushi; Satoh, Shigeru; Tsuchiya, Norihiko; Habuchi, Tomonori
• Is Part Of: Cancer letters. Volume 397(2017)
• Page Start: 103
• Page End: 110
• Publication Date: 2017-07-01
• Subjects: Prostate cancer -- Castration -- Bone metastasis -- Osteoclast -- Osteoprotegerin -- Receptor activator of nuclear factor kappa-B ligand; ADT androgen deprivation therapy -- ANOVA analysis of variance -- AR androgen receptor -- BMAs bone-modifying agents -- BMD bone mineral density -- CRPC castration-resistant prostate cancer -- CT computed tomography -- ELISA enzyme-linked immunosorbent assay -- HSPC hormone-sensitive prostate cancer -- OPG osteoprotegerin -- RANK receptor activator of nuclear factor kappa-B -- RANKL receptor activator of nuclear factor kappa-B ligand -- TRAP tartrate-resistant acid phosphatase; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.03.034
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Androgen deprivation therapy (ADT) for patients with metastatic or locally advanced prostate cancer reduces bone mineral density by stimulating receptor activator of nuclear factor kappa-B (RANK) signaling in osteoclasts. The involvement of the RANK/RANKL signaling in ADT-induced acceleration of bone metastasis in castration-insensitive prostate cancer was examined in a murine model using osteoprotegerin (OPG). Male Balb/c nude mice were divided into three groups: the non-castration, castration, and castration + OPG groups. PC-3M-luc-C6 was injected into the left ventricle of the mice. Recombinant OPG was injected intravenously twice weekly in the castration + OPG group. In-vivo imaging system (IVIS ® ) determined that the prevalence and photon counts of bone metastasis in the castration group were significantly higher than that in the non-castration and castration + OPG groups. The mean number of RANKL-positive osteoblasts and the mean serum RANKL level in the castration group were significantly higher than those in the non-castration group. RANKL-enhanced activation of osteoclasts was attenuated in the castration + OPG group. These results suggest that the mechanisms of RANK/RANKL signaling are involved in the ADT-induced acceleration of bone metastasis in castration-insensitive prostate cancer. Highlights: Castration reduced murine bone mineral density mediated by osteoclast activation. Castration accelerated bone metastasis of castration-insensitive prostate cancer PC3. Osteoprotegerin attenuated the castration-induced acceleration of bone metastasis. Castration-induced acceleration of bone metastasis involved RANK/RANKL signaling.