NF-κB signaling and integrin-β1 inhibition attenuates osteosarcoma metastasis via increased cell apoptosis

Osteosarcoma is a common primary bone malignancy, and distant metastasis limited the cure estimate during last decades. Detailed investigation of osteosarcoma metastasis is valuable for improving therapeutic strategy. Our study indicated increased integrin-β1 expression and NF-kB signaling activation in metastatic osteosarcoma tissues. Gain-of-function assays showed that integrin-β1 knockdown significantly inhibited osteosarcoma growth and metastasis, whereas exogenous reintroducing of integrin-β1 restored cell proliferation and metastasis in vitro and in vivo. NF-κB signaling directly modulated integrin-β1 expression, which is an effective target for the treatment of osteosarcoma. Mechanically, integrin-β1 blockage with AIIB2 antibody increased osteosarcoma cell apoptosis. Immunohistochemistry staining of integrin-β1 revealed that elevated integrin-β1 expression was correlated with poor prognosis of osteosarcoma patients and acted as an independent detrimental factor for osteosarcoma. Our data showed that integrin-β1 and NF-κB signaling are promising therapeutic targets to improve the clinical outcome of osteosarcoma patients. The examination of integrin-β1 expression will also identify patients with high risk of disease progression.