Different prostate cancer bone metastasis models respond differently to treadmill exercise (Abstract only)

Background: Prostate cancer (PCa) is a leading cause of death in men with a predilection to metastasize into bone, when the disease is considered to be uncurable. Exercise has been suggested to improve the health of patients with PCa but no current studies on its effects on PCa bone metastasis. Hypothesis: Treadmill exercise can prevent the progression of PCa bone metastasis. Methods: Human xenograft PCa cell line PC3 and murine syngeneic RM1-BM cells were intracardiacally injected (~1x10 cells/injection) into BALB/c nude (n=8) and C57BL/6J mice (n=12), respectively. The following day, the mice were subjected to treadmill exercise (12 meters/minute, 5° inclination, 30 minutes/day, 5 days/week) for 3 weeks. Bioluminescence assay was used to track skeletal tumour growth weekly and micro-CT was used to analyse bone morphometrics ex vivo. Naïve mice (n>6) were subject to the same treadmill protocol and used to assess the osteogenic response. Animal procedures were ethically approved by The University of Sheffield, UK. Results: In the xenograft model, the treadmill exercised mice developed significantly higher tumour burden (p< 0.05, Mann-Whitney test) in their hindlimbs compared to sedentary controls. The bone structure was not improved by treadmill exercise according to micro-CT analysis. In contrast, the syngeneic model showed significantly lower tumour burden in exercised mice compared to controls (p< 0.05, Mann-Whitney test) and a tendency to significantly improved survival curve (p=0.07, Gehan-Breslow-Wilcoxon test). The trabecular thickness (Tb.Th) was found significantly higher compared to controls (p< 0.001, unpaired t-test). In the naïve baseline study, the trabecular BV/TV had a 7.5% increase in C57BL/6J but 8.5% reduction in BALB/c nude mice, compared between exercised to sedentary controls. Conclusion: Treadmill exercise alleviates PCa growth in bones of syngeneic RM1-BM/C57BL/6J but not the xenograft PC3/BALB/c nude model, a possible consequence of different osteogenic response to treadmill by the two mouse strains.