Mechanical Stimulation Modulates Osteocyte Regulation of Cancer Cell Phenotype

Breast and prostate cancers preferentially metastasise to bone tissue, with metastatic lesions forming in the skeletons of most patients. On arriving disseminated tumour cells enter a mechanical microenvironment that is substantially different primary largely regulated by cells. Osteocytes, ubiquitous cell type, orchestrate healthy remodelling response physical exercise. However, effects loading osteocytes on cancer behaviour still poorly understood. The aim this study was characterise osteocyte stimulation breast To replicate an osteocyte-controlled environment, treated (MDA-MB-231 MCF-7) (PC-3 LNCaP) lines conditioned media from MLO-Y4 osteocyte-like exposed form fluid shear stress. We found paracrine signalling acted inhibit growth, characterised reduced proliferation invasion increased migration. In cells, these were reversed osteocytes. contrast, mechanically stimulated had no effect further investigate interactions, we developed microfluidic organ-chip model using Emulate platform. This new enabled analysis migration, presence stress, resulting These findings demonstrate importance regulating need incorporate factors into predictive vitro models metastasis.