CDH2 and metastatic neoplasm: As mechanism of epithelial mesenchymal transformation (EMT) and effect of PD-L1 immunosuppression play a pivotal role in tumor metastasis, we hypothesize osteosarcoma stimulates the metastatic process by releasing exosomes which carry large amount of PD-L1 and N-cadherin to help the progression and migration of metastatic tumors (Fig. 5a).