Monocyte chemotactic protein 1 promotes lung cancer-induced bone resorptive lesions in vivo.

摘要: Abstract Lung cancer is the leading cause of cancer-related deaths. The morbidity and mortality lung have markedly increased in past decade with at least 75% patients having evidence metastases time diagnosis. It frequently metastasizes to bone resulting osteolytic lesions unknown mechanisms. aim this study was identify factors that mediate cancer–induced osteoclast activity vivo . Using a human cytokine antibody array, we first determined levels conditioned medium collected from non– small cell A549 H1299 cells non-neoplastic bronchial epithelial BEAS2B cells. Both H1229 produced significantly higher amount several cytokines including monocyte chemotactic protein 1 (MCP-1) interleukin 8 (IL-8) compared These findings were confirmed by ELISA. From clinical serum specimens, also observed MCP-1 IL-8 localized tumor. Next, investigated effects on formation vitro using murine marrow–derived monocytes. induced inhibited neutralizing antibodies against MCP-1. Finally, stably transfected short hairpin RNA. knockdown implanted into tibia severe combined immunodeficient mice for 4 weeks. diminished growth. We conclude promotes thus resorptive