Fig. 4

Cell communication between breast cancer cells, osteoblasts and osteoclasts and a vicious circle. Breast cancer cells activate osteoblasts through direct cell–cell interactions and secretion of PTHrP. Osteoblasts, in turn, secrete RANKL to promote osteoclasts differentiation and bone resorption. When bone matrix is resorbed, TGF β, IGF1, and Ca²⁺ are released, promoting the invasion of breast cancer cells