Bone metastasis is a common complication of certain cancers such as melanoma. The spreading of cancer cells into the bone is supported by changes in the bone marrow environment. The specific role of osteocytes in this process is yet to be defined. By RNA-seq and chemokines screening we show that osteocytes release the chemokine CXCL5 when they are exposed to melanoma cells. Osteocytes-mediated CXCL5 secretion enhanced the migratory and invasive behaviour of melanoma cells. When the expression of the CXCL5 receptor, CXCR2, was down-regulated in melanoma cells in vitro, we observed a significant decrease in melanoma cell migration in response to osteocytes. Furthermore, melanoma cells with down-regulated CXCR2 expression showed less bone metastasis and less bone loss in the bone metastasis model in vivo. Furthermore, when simultaneously down-regulating CXCL5 in osteocytes and CXCR2 in melanoma cells, melanoma progression was abrogated in vivo. In summary, these data suggest a significant role of osteocytes in bone metastasis of melanoma, which is mediated through the CXCL5-CXCR2 pathway.

中文翻译：

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骨细胞通过CXCL5支持黑色素瘤细胞骨转移

骨转移是某些癌症（例如黑色素瘤）的常见并发症。骨髓环境的变化支持癌细胞扩散到骨骼中。骨细胞在此过程中的具体作用尚待确定。通过 RNA-seq 和趋化因子筛选，我们发现骨细胞在暴露于黑色素瘤细胞时会释放趋化因子 CXCL5。骨细胞介导的 CXCL5 分泌增强了黑色素瘤细胞的迁移和侵袭行为。当黑色素瘤细胞中 CXCL5 受体 CXCR2 的表达在体外下调时，我们观察到黑色素瘤细胞响应骨细胞的迁移显着减少。此外，在体内骨转移模型中，CXCR2表达下调的黑色素瘤细胞显示出较少的骨转移和较少的骨丢失。此外，当同时下调骨细胞中的CXCL5和黑色素瘤细胞中的CXCR2时，体内黑色素瘤的进展被消除。总之，这些数据表明骨细胞在黑色素瘤骨转移中发挥重要作用，这是通过 CXCL5-CXCR2 途径介导的。