Fig. 2

Schematic illustration of main OPG sources and actions in breast tumorigenesis. According to most pre-clinical findings, OPG produced by breast cancer and endothelial cells is able to promote tumor growth at the primary tumor site, as well as development of metastatic tumors at extra-skeletal sites, through distinct mechanisms: a inhibition of the monocyte-derived apoptosis inducing factor TRAIL, b increased expression of some proteases (e.g. cathepsin D, matrix metalloproteinase-2), c induction of endothelial cells proliferation and differentiation to form new blood vessels (angiogenesis). Conversely, OPG produced in bone microenvironment can mitigate intra-osseous tumor growth and prevent breast cancer-induced osteolysis by reducing differentiation and activation of mature osteoclasts lining the bone surface. Abbreviations: OPG, osteoprotegerin; TRAIL, TNF related apoptosis-inducing ligand. Adapted from Weichhaus et al., Mol Cancer (ref. [31])