Reduction of breast cancer extravasation via vibration activated osteocyte regulation.

ABSTRACT

Physical exercise benefits breast cancer patients by reducing cancer progression and promoting bone health. However, intense exercise is physically challenging for bedridden, disabled, or aged patients. As an exercise surrogate, low-magnitude (<1 g) high-frequency (>30 Hz) (LMHF) vibration has gained growing interest in recent years, but its effects on bone metastasis remain unknown. We used a microfluidic co-culture platform that mimics bone-cancer environments to study the impact of vibration on breast cancer extravasation. LMHF vibration activated osteocytes, the primary mechanosensing cells in bones, which reduced cancer extravasation by 43%. We further studied the vibration mechanism by demonstrating the important role of the Piezo1 ion channel in osteocyte mechanotransduction. Chemical activation of Piezo1 enhanced osteocyte inhibition of cancer extravasation under vibration at the early time point. These data indicated that LMHF vibration could inhibit cancer extravasation, suggesting that vibration may suppress bone metastasis in breast cancer patients.