Figure 2.

Schematic diagram of the interaction between the bone microenvironment and tumor cells.

Tumor cells produce cytokines and growth factors which stimulate osteoclastogenesis, inducing an increase in bone resorption and the release of growth factors from the bone matrix. These factors stimulate proliferation, migration and angiogenesis of tumor cells. Bisphosphonates can break this vicious circle by inhibiting osteoclastogenesis and bone resorption. PTHrp = parathormone-related protein; PGE = prostaglandin E; RANKL = receptor activator of nuclear factor κβ ligand; OPG = osteoprotegerin; PDGF = platelet derived growth factor; IGF = insulin-like growth factor; IL = interleukin.