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.