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

Author:
Li, Rui, Shi, Yanlong, Zhao, Shiwei, Shi, Tingting, Zhang, Guichun
Source:
International journal of biological macromolecules 2019 v.123 pp. 1035-1043
ISSN:
0141-8130
Subject:
CD29 antigen, antibodies, apoptosis, cell proliferation, gain-of-function mutation, immunohistochemistry, metastasis, osteosarcoma, patients, prognosis, risk, staining, therapeutics, tissues, transcription factor NF-kappa B
Abstract:
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.
Agid:
6226806