Elucidation of the mechanisms regulating bone metastasis and invasion via the interaction between tumor and bone microenvironment.

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We identify receptor activator of nuclear factor κB ligand (RANKL) as a tumor microenvironment-specific factor essential for high affinity to bone via integrin upregulation and the following osteoclast differentiation, utilizing oral squamous cell carcinoma as a model. In addition, in human synovial sarcoma that frequently occurs bone metastasis, the interaction between the tumor and endothelial cells promotes tumor angiogenesis, through Src famiy kinase-dependent VEGF expression in the tumor cells.