Figure 1
The vicious circle at the bone remodeling unit. Tumor cells produce factors that increase the formation of osteoclasts through
the RANK-RANKL (receptor activator of nuclear factor-κB ligand) system: IL-6 (interleukin-6), prostaglandin E2 (PGE2), tumor
necrosis factor (TNF), macrophage colony-stimulating factor (M-CSF), and parathyroid hormone-related peptide (PTH-rP). During
bone resorption, osteoclasts release transforming growth factor-β (TGF-β), insulin-like growth factors (IGFs), fibroblast
growth factors (FGFs), platelet-derived growth factor (PDGF), and bone morphogenetic proteins (BMPs), which increase the production
of parathyroid hormone-related peptide by tumor cells, as well as growth factors that increase tumor growth. This represents
the vicious circle that increases bone destruction and tumor growth. OPG, osteoprotegerin. Adapted from (Clamp et al. 2004, Roodman 2004).