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Abstract. Approximately 25% of osteosarcoma patients present with clinically detectable metastatic disease at the time of initial diagnosis. High-dose chemotherapy and/or surgery for the treatment of primary metastatic osteosarcoma is ineffective, and <20% of patients will survive 5 years from diagnosis. Therefore, the treatment of metastases is critical for the improvement of the prognosis of primary metastatic osteosarcoma patients. We have previously observed that overexpression of interleukin-24 (IL-24) inhibits neuroblastoma cell proliferation, migration and invasion in vitro. The present study investigated whether IL-24 may be a novel agent for osteosarcoma metastasis-suppressive treatment. It was observed that IL-24 is able to inhibit migration and invasion in spontaneously metastasizing human 143B osteosarcoma cells via the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway. IL-24 was effective in inhibiting JNK and c-Jun phosphorylation to downregulate matrix metalloproteinase (MMP)-2 and MMP-9, which contributed to the suppression of cell migration and invasion. It was concluded that IL-24 may be a potent agent in the inhibition of highly metastatic 143B osteosarcoma cells, and IL-24 may have translational potential as an effective therapeutic agent for the treatment of metastatic osteosarcoma.

Neuroblastomas are common pediatric solid tumors with a variable clinical course; approximately 50% of patients present with metastatic disease at diagnosis. The development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of metastases during the early stage of tumor development is critical for the improvement of the prognosis of neuroblastoma patients. We previously observed the suppression of neuroblastoma growth in response to overexpression of interleukin-24 (IL-24) in vitro and in vivo. IL-24 exerts its tumor-suppressive effects by multiple mechanisms, including the balance of Bcl-2 family proteins toward the pro-apoptotic pathway and the activation of the caspase cascade. In this study, we used adenovirus-mediated IL-24 (Ad-IL24) to examine the effect of the ectopic production of IL-24 on cell migration and invasion in human neuroblastoma cells. We found that IL-24 effectively inhibits SH-SY5Y neuroblastoma cell migration and invasion by changing subcellular localization and cellular levels of β-catenin and regulating the levels of proteins associated with cell migration and invasion. Thus, IL-24 should be considered a therapeutic agent that can inhibit primary neuroblastoma growth and that may prevent metastasis.