[PDF] A novel mechanobiological model of bone metastasis reveals that mechanical stimulation inhibits the pro-osteoclastogenic effects of breast cancer cells-论文阅读讨论-ReadPaper

摘要

Tumor metastasis into bone alters the biomechanical cues experienced by both tumor and native bone cells (osteoblasts, osteoclasts and osteocytes). Both bone and tumor cells are regulated by mechanical stimuli, yet the mechanobiological role bone and tumor cells play in driving osteolysis are unresolved. Here, 3D in vitro co-culture and computational models were developed to investigate the coupled influence of tumor-bone cell signaling and growth induced matrix stress on tumor growth. We then developed advanced in vitro 3D models of the in vivo multicellular and mechanical environment and confirmed the ability to recapitulate osteoblast, osteoclast and metastatic activity. We applied this bone metastasis model to investigate how interactions between tumor and bone cells, and their surrounding biophysical environment, dictate osteolysis and tumor development. Our results demonstrated that tumor spheroid growth is regulated by the synergistic influence of bone cell signaling and matrix stiffness. We also demonstrate, for the first time, that mechanical compression can attenuate breast cancer cell activity and reverse pro-osteoclastogenic activity during early-stage bone metastasis.

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