Schematic diagram of the cross-talk between MSCs and OS cells in the bone microenvironment. MSCs directly secrete some factors or choose the extracellular vesicles as the carrier to transport miRNAs, growth factor, lipids, glutamate, lactase, which promote OS metastasis. Meanwhile, OS utilizes the acidic environment, hypoxia and extracellular vesicles inducing the MSCs secreting cell factors to facilitate their own growth and metastasis, like IL-8, IL-6, RelA, RelB, NF-κB1, CSF2/GM-CSF, CSF3/G-CSF, BMP2, CCL5, CXCL5, CXCL1. In addition, OS via secreted MCP-1, GRO-α, and TGF-β induces MSCs trans-differentiating the cancer-associated stem cells to express more MCP-1. GRO-α, IL-6, and IL-8 promote the MAT of OS. The solid arrows refer to the direction of the cell or factor from the MSCs. The dotted arrows refer to the direction of cells and factors from OS.