MIF and osteosarcoma: In addition to hematopoietic stem cells, CXCR4 is expressed on various cell types, including macrophages, myeloid derived suppressor cells, and osteosarcoma cells.79-82 Downstream CXCR4 signaling is incredibly complex with context dependent crosstalk with other receptors and ligand-specific downstream signal transducers and effectors.80 In its most simplistic form, CXCL12/SDF1 and MIF comprise the two major CXCR4 signaling axes.