Vicious cycle in the generation of osteoclastic bone metastases in mammary cancer

This video describes the bone loss through metastases of breast cancer. The CXCL12 chemokine formed by stromal cells of the bone marrow binds to the CXCR4 receptor of the tumor cells, which migrate into the bone marrow along the chemokine gradient. IL-11 stimulates the synthesis of RANKL (RANK ligand) in osteoblasts. RANKL binds to RANK (Receptor Activator of NF-Kappa B) of osteoclast precursors and thus stimulates differentiation into osteoclasts. Differentiation from and activation of osteoclasts is enhanced by osteopontin. Matrix metalloproteases of osteoclasts and tumor cells (MMP1) release TGF-b from the bone matrix. TGF-b stimulates the synthesis of IL-11 and in this way maintains the vicious circle. The scheme is based on data from Kang et al. (2003). Cancer Cell 3, 537.