[摘要]：The development of pulmonary metastasis is the major cause of death in osteosarcoma, and its molecular basis is poorly understood. In this study, we show that beta 4 integrin is highly expressed in human osteosarcoma cell lines and tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased levels of beta 4 integrin. Suppression of beta 4 integrin expression by shRNA and disruption of beta 4 integrin function by transfection of dominant-negative beta 4 integrin was sufficient to revert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary tumor growth. These findings suggest a role for beta 4 integrin expression in the metastatic phenotype in human osteosarcoma cells. In addition, we identified a previously uncharacterized interaction between beta 4 integrin and ezrin, a membrane-cytoskeletal linker protein that is implicated in the metastatic behavior of osteosarcoma. The beta 4 integrin-ezrin interaction appears to be critical for maintenance of beta 4 integrin expression. These data begin to integrate ezrin and beta 4 integrin expression into a model of action for the mechanism of osteosarcoma metastases. Oncogene (2009) 28, 3401-3411; doi: 10.1038/onc.2009.206; published online 13 July 2009
