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

RANK是RANKL的受体，RANKL是破骨细胞形成所必需的分子。此前，我们曾报道Wnt5a-Ror2途径可增强巨噬细胞RANK的表达。另一方面，另一个研究小组报道，RANK在肿瘤细胞中的表达增强了骨转移。综上所述，这些发现表明，肿瘤细胞表达的Wnt以自分泌的方式影响自身，并通过诱导RANK表达促进骨转移。为了验证这一假说，我们使用与骨骼有亲和力的细胞系，如乳腺癌和前列腺癌细胞系进行实验。结果表明，与对照细胞相比，这些细胞表达RANK、WNT5a和Ror1/2。这些结果表明，肿瘤细胞表达的Wnt5a以自分泌方式作用于自身表达的Ror2，并通过诱导肿瘤细胞RANK表达来促进骨转移。

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.