Bone Abstracts

Cross talk between tumour cells and the host microenvironment plays a critical role in tumour progression. There have been multiple studies that have highlighted the importance of proteins secreted by tumour cells that then act on the tumour microenvironment and by proteins secreted by the host microenvironment that promote tumour progression at the metastatic niche. However, little is known regarding the role of physical forces on tumour progression.

Bone has several unique properties including calcified matrix and specialized cells including osteoclasts, osteoblasts and osteocytes. While the role of osteoclasts and osteoblasts have been described in the pathophysiology of bone metastases, there is a dearth of knowledge regarding the role of osteocytes in bone metastasis. Osteocytes are the most prevalent cell present in mineralized bone and are considered the main mechanotransducing cells. Thus it is plausible that osteocytes can respond to tumour-generated physical forces, which in turn induce signalling in the osteocytes resulting in their ability to impact tumour progression.

To test this possibility, it was determined if tumour-generated pressure modifies the bone metastatic niche to promote metastatic growth in a model of prostate cancer (PCa) bone metastasis. Pressure-transducing catheters were implanted into the tibiae of mice and pressure was monitored as tumours developed. Afterwards, osteocytes were subjected to similar pressures in vitro to determine the impact on their cytokine expression and the ability of pressure to modify osteocytes impact on PCa growth. PCa tumours growing in the tibiae of mice increased intraosseous pressure above basal levels. Application of similar levels of pressure to osteocytes induced their ability to promote PCa growth and invasion, in part, through up-regulating several chemokines, such as CCL5, and matrix metalloproteinase (MMP) production.

These studies demonstrate that physical forces can alter the tumour microenvironment to promote tumour growth and that osteocytes are important components that promote tumour growth in the bone metastatic niche. Further evaluation of the role of osteocytes and physical forces in tumour progression are warranted and could lead to identification of specific targets to minimize tumour progression.