Cancer Res：CXCL10促进肿瘤溶骨性骨转移

早期研究发现趋化因子CXCL10和RANKL具有促进破骨细胞分化和溶骨性骨转移作用，但在这些过程中，内源性CXCL10的功能却未得到研究。

近日，发表在Cancer Research杂志上的一则新研究中，研究人员揭示了内源性CXCL10对招募癌细胞至骨非常重要，能促进破骨细胞分化，是形成溶骨性骨转移的关键因子。

用中和抗体抑制CXCL10能降低迁移癌症细胞表达CXCL10的受体——CXCR3，CXCL10的缺失能减少体内骨肿瘤的负荷。肿瘤骨骼定向转移过程中宿主CXCL10的产生对癌细胞的生长和随后的溶骨是必须的。肿瘤细胞和巨噬细胞之间的直接互动进一步激发了巨噬细胞CXCL10的产生。骨骼转移肿瘤细胞的生长借助于CXCL10刺激癌细胞粘附I型胶原以及RANKL介导的破骨细胞的形成。

总之，研究结果证实CXCL10有助于表达CXCR3的癌细胞转移至骨，能促进破骨细胞的分化。

doi:10.1158/0008-5472.CAN-12-0481
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CXCL10 Promotes Osteolytic Bone Metastasis by Enhancing Cancer Outgrowth and Osteoclastogenesis

Jong-Ho Lee, Ha-Neui Kim, Kyung-Ok Kim, Won Jong Jin, Seungbok Lee, Hong-Hee Kim, Hyunil Ha, and Zang Hee Lee

Amplification of the chemokines CXCL10 and RANKL has been suggested to promote osteoclast differentiation and osteolytic bone metastasis, but a function for endogenous CXCL10 in these processes is not well established. In this study, we show that endogenous CXCL10 is critical to recruit cancer cells to bone, support osteoclast differentiation and promote for the formation of osteolytic bone metastases. Neutralizing CXCL10 antibody reduced migration of cancer cells expressing the CXCL10 receptor CXCR3, and loss of CXCR3 or CXCL10 decreased bone tumor burden in vivo. Bone colonization augmented host production of CXCL10, which was required for cancer growth and subsequent osteolysis. Direct interactions between cancer cells and macrophages further stimulated CXCL10 production from macrophages. Growth of bone metastases required CXCL10-stimulated adhesion of cancer cells to type I collagen as well as RANKL-mediated osteoclast formation. Together, our findings show that CXCL10 facilitates trafficking of CXCR3-expressing cancer cells to bone, which augments its own production and promotes osteoclastic differentiation. CXCL10 therefore may represent a therapeutic target for osteolytic bone metastasis.