Crosstalk between Metastatic Cancer Cells and Bone Microenvironments

Bone is one of the most preferential target sites for cancers such as breast, prostate and lung cancers to metastasize. Although the mechanism underlying this organ preference still needs to be elucidated, observations

Bone is one of the most preferential target sites for cancers such as breast, prostate and lung cancers to metastasize. Although the mechanism underlying this organ preference still needs to be elucidated, observations that specific inhibitors of osteoclasts such as bisphosphonates inhibit bone metastases suggest a critical role of osteoclasts. Bone provides favorable microenvironments that allow cancer cells to arrest, colonize and survive. Bone stores large amounts of growth factors including IGFs and TGFα that are continuously released into the bone marrow cavity as a consequence of osteoclastic bone resorption in physiological conditions. Osteoclasts also assist cancer ceils to invade bone by destroying hard mineralized tissue, Thus,bone is a fertile soil for metastatic cancer cells and the degree of osteoclastic bone resorption is likely critical to the development and progression of bone metastases. Consistent with this notion, stimulation of osteodastic bone resorption by the administration of RANKL,