fig4

Figure 4. Sphingosine 1-phosphate (S1P) activity in bone metastasis microenvironment: overview of actions of S1P on bone cells, cancer cells, and adipocytes. Black arrows indicate activities of S1P, receptor-activated NF-κB ligand (RANK-L), and tumor growth factor β (TGFβ) on different cell types from the bone microenvironment (names in orange) resulting in multiple biological functions (text in white). Grey arrows indicate S1P and RANK-L secretions and TGFβ release from resorbed bone matrix. Dotted black arrows indicate cell differentiation (adipogenesis and osteoblastogenesis). Red lines indicate S1P and Calcitonin inhibitory activities.