A novel mechanobiological model of bone metastasis reveals that mechanical stimulation inhibits the pro-osteoclastogenic effects of breast cancer cells

Bone is highly susceptible to cancer metastasis, and both tumour and bone cells enable tumour invasion through a "vicious cycle" of biochemical signalling. Tumor metastasis into bone also alters biophysical cues to both tumour and bone cells, which are highly sensitive to their mechanical environment. However, the mechanobiological feedback between these cells that perpetuates this cycle has not been studied. Here, we develop highly novel in vitro and computational models to provide an advanced understanding of how tumor growth is regulated by the synergistic influence of tumour-bone cell signaling and mechanobiological cues. In particular, we develop the first multicellular healthy and metastatic bone models, which can account for physiological mechanical signals within a custom bioreactor. These models successfully recapitulated mineralization, mechanobiological responses, osteolysis and metastatic activity. Ultimately we demonstrate that mechanical stimulus provided protective effects against tumor-induced osteolysis, confirming the importance of mechanobiological factors in bone metastasis development.