Prolonged Antiresorptive Treatment of Lytic Prostate Cancer Xenografts in Mouse Bone Results in Tumor Necrosis

J. M. Blair ； J. R. K. Modzelewski ； L. A. Perryman ； P. J. Russell ； M. J. Seibel ； C. R. Dunstan

《Journal of Cancer Molecules》 4卷6期 (2009/02) Pp. 175-181

https://doi.org/10.29685/JCM.200902.0003

並列摘要

AIM: In this study, we examine the time dependence of commencing antiresorptive treatments, using an Fc-fusion osteoprotegerin construct (Fc-OPG), on the growth, viability and lytic effects of PC3 human prostate cancer xenografts in male mouse bone.
METHODS: Male mice were implanted with PC3 cells by intratibial injection. Mice were randomized into three groups (n=5-7 per group) to receive vehicle or 3 mg/kg Fc-OPG three times weekly from the week before cell injection (week-1; early treatment), week 0 (simultaneous treatment) or week 2 (delayed treatment).
RESULTS: When compared with vehicle-treated controls, Fc-OPG treatments protected bone and reduced bone turnover marker levels. In early and simultaneous Fc-OPG treated mice, necrosis of bone-enclosed tumor and the adjacent endosteal bone was observed. No tissue or bone necrosis was seen in sham-injected or vehicletreated controls or in the contralateral tibiae of Fc-OPG treated mice.
CONCLUSION: The necrosis of bone-confined tumor in Fc-OPG-treated mice suggests that prolonged blockage of bone erosion during the early development of a tumor mass in bone can limit vascular supply, leading to necrosis. The loss of osteocyte viability was only seen adjacent to necrotic tumor, which suggests that this effect is not due to bone resorption inhibition per se but to interactions between inhibition of bone resorption and tumor effects.

並列關鍵字

osteoprotegerin ； bone resorption ； bone metastasis ； RANK ligand