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- Title
Treadmill Running Suppressed Breast Cancer Bone Metastasis by Altering Cytokine-related Systemic Effects Rather Than Direct Osteogenic Response.
- Authors
Latif, Norain Binti Ab.; Ning Wang; Gartland, Alison
- Abstract
Introduction: Breast cancer (BC) bone metastasis often leads to progressive bone damage caused by heightened osteoclastic resorption. Studies show direct bone loading inhibited tumour growth and osteolytic progression in established bone metastasis models mediated by loading-induced osteogenic response. Several preclinical studies showed treadmill running (TR) inhibited primary tumour growth by modulating systemic factors such as inflammatory cytokines and host anti-tumour immunity, but no study has shown whether TR could prevent bone metastases in BC models. This study aims to investigate whether TR exercise prevent and inhibit bone metastases in BC mouse models. Methods: Eight-week-old female BALB/c were subjected to TR at 12m/min, 5° incline, 30 min/day, 5 days/ week for 1 week. Mice were then randomised into naïve, TR and control groups, with the TR and control groups being intracardially injected with murine 4T1-Luc2 cells and the TR group continued exercise for another 2 weeks. Tumour growth was monitored by bioluminescence imaging. After 3 weeks of running, all mice were euthanized, the femurs were micro-CT scanned and subsequently sectioned and stained for analysis. Bone turnover markers and cytokines were measured in the serum samples and immunohistochemistry staining was performed on the femur sections of the naïve mice. Results: TR lowered the occurrence of bone metastasis (28%, p=0.0455), prolonged the survival of tumour-bearing mice (67% vs. 33%), reduced bone metastatic tumour burden (36%, p=0.0019) and the percentage of lesion area (53%, p=0.0072) and potentially protected bone against tumour-induced bone loss. In naïve mice, the same TR regimen was not osteogenic, however serum analysis revealed TR lowered the levels of many inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Immunostaining also demonstrated lower expression of IL-1β in the femur of TR naïve mice. Conclusion: TR could potentially prevent and inhibit bone metastasis via modulation of inflammatory cytokine-related systemic effect rather than direct osteogenic response.
- Subjects
BONE metastasis; TREADMILLS; BLOOD serum analysis; BONE remodeling; X-ray computed microtomography
- Publication
Malaysian Journal of Medicine & Health Sciences, 2024, Vol 20, p61
- ISSN
1675-8544
- Publication type
Abstract