BoneKEy Reports | BoneKEy Watch
CXCL10 is a key player in osteolytic bone metastasis
DOI:10.1038/bonekey.2012.146
CXCL10, a chemokine that induces interferon γ (IFN-γ), is known to recruit Th1 cells and to upregulate IFN-γ production during inflammation. In bone, CXCL10 recruits CD4+ T cells, stimulating them to produce RANKL, which then promotes osteoclast differentiation. This study sought to discover more about the potential role of CXCL10 in bone metastasis.
In mice, an intraperitoneal injection of sRANKL induced the migration of several cancer cell lines to bone, reducing CXCR3 expression in cancer cells and thereby inhibiting CXCL10 signaling. It also decreased the number and size of metastatic bone tumors that developed. The role of CXCL10 in bone metastasis was confirmed by comparing wild type and CXCL10 knockout mice: CXCL10−/− mice had significantly fewer bone metastases in both the hind limbs and the mandibular region.
Further studies showed that CXCL10 mediated the direct interaction between cancer cells expressing the CXCR3 receptor and bone marrow macrophages. This interaction, in turn, augmented CXCL10 levels still further, enabling it to promote differentiation of osteoclasts.
Editor's comment: This study provides compelling evidence that chemokine CXCL10 and its receptor, CXCR3, play a critical role in mediating cancer cell dissemination to the skeleton and in stimulating osteoclastic differentiation. Further exploration of CXCL10 as a therapeutic target in osteolytic bone metastasis is warranted.
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