Tumor-derived microparticles promoted M2-like macrophages polarization to stimulate osteosarcoma progression.

Microparticles (MPs) are a heterogeneous subpopulation of extracellular vesicles that originate from the plasma membranes of cells. There is increasing evidence that tumor-derived MPs (T-MPs) play a significant role in tumor progression and immune response in cancer. In our study, we found an increased secretion of MPs in osteosarcoma tissues obtained from metastatic patients. These T-MPs promoted polarization of M2-like macrophages and stimulated the migration and chemoresistance of osteosarcoma cells. Mechanistically, T-MPs promoted macrophage polarization to an M2-like phenotype through TBK1-STAT6 signaling. Consequently, these M2-like macrophages mediated osteosarcoma cell migration via CCL18/STAT3 signaling. Blockade of STAT3 signaling pathway improved the outcome of chemotherapy in LM8-bearing osteosarcoma mice model. Thus, our study reveals how tumor cells regulate macrophage polarization by releasing MPs and provides new insights into clinical osteosarcoma therapy.