Osteoprotegerin expression during the micro- and macrometastatic phases of the osteoblastic metastasis in prostate cancer: therapeutic implications

Introduction: Osteoprotegerin (OPG) acts as a soluble decoy receptor for the bone marrow stroma cell-derived and osteoblast-derived receptor activator of nuclear factor-kB ligand (RANKL), thus regulating the RANK-mediated osteoclastogenesis and osteoclast-mediated bone resorption at the metastatic niche of cancer in skeleton. Areas covered: This article discusses the 'key' role of OPG expression during the early events of cancer cell invasion into the bone matrix and the subsequent events underlying the formation of osteoblastic metastasis, a unique event observed in human prostate cancer biology. Expert opinion: Understanding the cellular and molecular events implicated in bone metastasis can facilitate designing new therapeutic strategies for targeting early and/or late events in the metastasis processes. The RANKL/RANK/OPG pathway is a key regulator of pathological bone metabolism in metastatic sites. Targeted manipulation of these molecules may provide sustainable antitumor responses.