Pathological Crosstalk between Metastatic Breast Cancer Cells and the Bone Microenvironment

Bone is the most common metastatic site in breast cancer. Upon arrival to the bone, disseminated tumor cells can undergo a period of dormancy but often eventually grow and hijack the bone microenvironment. The bone marrow microenvironment consists of multiple cell types including the bone cells, adipocytes, endothelial cells, and nerve cells that all have crucial functions in the maintenance of bone homeostasis. Tumor cells severely disturb the tightly controlled cellular and molecular interactions in the bone marrow fueling their own survival and growth. While the role of bone resorbing osteoclasts in breast cancer bone metastases is well established, the function of other bone cells, as well as adipocytes, endothelial cells, and nerve cells is less understood. In this review, we discuss the composition of the physiological bone microenvironment and how the presence of tumor cells influences the microenvironment, creating a pathological crosstalk between the cells. A better understanding of the cellular and molecular events that occur in the metastatic bone microenvironment could facilitate the identification of novel cellular targets to treat this devastating disease.