The analysis of the effect of novel agent for bone metabolism on bone metastasis

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RANK is a receptor of RANKL which is an essential molecule for osteoclastogenesis. Previously, we reported that the Wnt5a-Ror2 pathway enhances the expression of RANK in macrophages. On the other hand, another group reported that the expression of RANK in tumor cells enhance bone metastasis. Taken together, these findings suggest that the Wnt expressed by tumor cells affects itself in an autocrine manner, and promotes bone metastasis through the induction of RANK expression.To test this hypothesis, we performed experiments using cell lines which have affinity for the bone such as breast and prostate cancer cell lines. In results these cells highly expressed RANK, Wnt5a and Ror1/2 in comparison with control cells. These results indicate that Wnt5a expressed by tumor cells act on Ror2 expressed in itself in an autocrine manner, and enhanced bone metastasis through the induction of RANK expression in tumor cells.