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CXCL10 promotes osteolytic bone metastasis by enhancing cancer outgrowth and osteoclastogenesis.

Cited 64 time in Web of Science Cited 68 time in Scopus
Issue Date
2012-07
Publisher
American Association for Cancer Research
Citation
CANCER RESEARCH Vol.72 No.13, pp. 3175-3186
Keywords
의약학
Abstract
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. Cancer Res; 72(13); 3175-86. ⓒ2012 AACR.
ISSN
0008-5472
Language
English
URI
https://hdl.handle.net/10371/82238
DOI
https://doi.org/10.1158/0008-5472.CAN-12-0481
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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