Fig. 1

Vicious circle in the bone microenvironment of bone metastatic prostate cancer. Prostate cancer cells secrete TGFβ, IGF, PDGF, EDN1, uPA, and VEGF, which regulate osteoblast proliferation and/or differentiation. Osteoblasts secrete RANKL and IL-6 to activate osteoclasts, while OPG can inhibit the activation of osteoclasts, which elicits bone resorption and secrete EGF and calcium, thereby stimulating cancer cell proliferation in bone. Abbreviations: TGFβ, transforming growth factor β; IGF, insulin-like growth factor; PDGF, platelet-derived growth factor; EDN1, endothelin 1; uPA, urokinase plasminogen activator; VEGF, vascular endothelial growth factor; RANKL, receptor activator of the nuclear factor-κB ligand; IL-6, interleukin 6; OPG, osteoprotegerin; EGF, epidermal growth factor