Prostate cancer bone metastases promote both osteolytic and osteoblastic activity

AbstractAdvanced prostate cancer is frequently accompanied by the development of metastasis to bone. In the past, prostate cancer bone metastases were characterized as being osteoblastic (i.e., increasing bone density) based on radiographs. However, emerging evidence suggests that development of prostate cancer bone metastases requires osteoclastic activity in addition to osteoblastic activity. The complexities of how prostate tumor cells influence bone remodeling are just beginning to be elucidated. Prostate cancer cells produce a variety of pro‐osteoblastic factors that promote bone mineralization. For example, both bone morphogenetic proteins and endothelin‐1 have well recognized pro‐osteoblastic activities and are produced by prostate cancer cells. In addition to factors that enhance bone mineralization prostate cancer cells produced factors that promote osteoclast activity. Perhaps the most critical pro‐osteoclastogenic factor produced by prostate cancer cells is receptor activator of NFκB ligand (RANKL), which has been shown to be required for the development of osteoclasts. Blocking RANKL results in inhibiting prostate cancer‐induced osteoclastogenesis and inhibits developme