Bone: A Fertile Soil for Cancer Metastasis.

Bone is one of the most common and most dangerous sites for metastatic growth across cancer types, and bone metastasis remains incurable. Unfortunately, the processes by which cancers preferentially metastasize to bone are still not well understood. In this review, we summarize the morphological features, physical properties, and cell signaling events that make bone a unique site for metastasis and bone remodeling. The signaling crosstalk between the tumor cells and bone cells begins a vicious cycle - a self-sustaining feedback loop between the tumor cells and the bone microenvironment composed of osteoclasts, osteoblasts, other bone marrow cells, bone matrix, and vasculature to support both tumor growth and bone destruction. Through this crosstalk, bone provides a fertile microenvironment that can harbor dormant tumor cells, sometimes for long periods, and support their growth by releasing cytokines as the bone matrix is destroyed, similar to providing nutrients for a seed to germinate in soil. However, few models exist to study the late stages of bone colonization by metastatic tumor cells. We describe some of the current methodologies used to study bone metastasis, highlighting the limitations of these methods and alternative future strategies to be used to study bone metastasis. While <i>in vivo</i> animal and patient studies may provide the gold standard for studying metastasis, <i>ex vivo</i> models can be used as an alternative to enable more controlled experiments designed to study the late stages of bone metastasis.