Figure 1.

Interleukins during the progression of breast cancer bone metastasis. Interleukins (ILs) play pivotal roles in mediating several steps of the metastatic cascade in breast cancer. Dynamic changes in circulating tumor cell (CTC) levels in combination with corresponding alterations in serum IL levels might serve as prognostic markers for the progression of breast cancer. Furthermore, ILs are suggested to regulate the attraction of disseminated tumor cells (DTCs) to the metastatic site, facilitate extravasation from the circulation, adhesion and migration in the secondary organ. Once in the secondary organ, DTCs receive interleukin signals from adjacent, tissue-resident cells that regulate their fate in the secondary organ. Cells of the bone microenvironment secrete ILs that control tumor cell dormancy. In turn, proliferating tumor cells secrete ILs that stimulate osteoclastic bone resorption and consequently osteolysis. Factors released during osteolysis (e.g., Transforming growth factor β (TGF-β)) then fuel the vicious cycle of bone metastasis. Stromal-derived ILs can also regulate tumor growth via affecting vascular endothelial cells, thus promoting vascularization and metastatic growth.