In vivo, IL-6 increased the growth of tumors formed from osteosarcoma CSCs, and elevated the levels of OPN and p-STAT3 (P < 0.05; Fig. 6) Our data suggest that IL-6 promotes osteosarcoma CSC-like features and chemoresistance by activating STAT3 via OPN in vitro and in vivo. This evidence concerns the gene SPP1 and osteosarcoma.