Figure 1.
Breast cancer bone metastases. When active TGF-β is released from the bone matrix upon bone resorption by osteoclasts it acts on breast cancer cells to stimulate the production of osteolytic factors, such as parathyroid hormone-related protein (PTHrP), connective tissue growth factor (CTGF) and interleukin-(IL) 6 and −11. These factors increase the RANKL/OPG expression ratio in osteoblasts, which bind to the RANK receptors expressed on osteoclasts and activate osteoclastogenesis. TGF-β can directly stimulate osteoclast activity and inhibiting osteoblast differentiation thus, TGF-β can stimulate tumor growth.