CXCL10 Promotes Osteolytic Bone Metastasis by Enhancing Cancer Outgrowth and Osteoclastogenesis
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...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2012-07, Vol.72 (13), p.3175-3186 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | LEE, Jong-Ho KIM, Ha-Neui KIM, Kyung-Ok WON JONG JIN LEE, Seungbok KIM, Hong-Hee HYUNIL HA ZANG HEE LEE |
| description | 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. |
| doi_str_mv | 10.1158/0008-5472.can-12-0481 |
| format | Article |
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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.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-12-0481</identifier><identifier>PMID: 22562465</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; Bone Neoplasms - secondary ; Cell Differentiation - physiology ; Cell Line ; Cell Line, Tumor ; Chemokine CXCL10 - physiology ; Diseases of the osteoarticular system ; Enzyme-Linked Immunosorbent Assay ; Humans ; Medical sciences ; Mice ; Osteoclasts - pathology ; Osteolysis ; Pharmacology. 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CXCL10 therefore may represent a therapeutic target for osteolytic bone metastasis.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Bone Neoplasms - secondary</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Chemokine CXCL10 - physiology</subject><subject>Diseases of the osteoarticular system</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Osteoclasts - pathology</subject><subject>Osteolysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><subject>Tumors of striated muscle and skeleton</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1LwzAUQIMobk5_gpIXwZfO5Cbp2sdZ5gdM54OCbyFJ063SNTPpkP17UzYVApfAOffCQeiSkjGlIrslhGSJ4BMYG9UmFBLCM3qEhlSwLJlwLo7R8I8ZoLMQPuNXUCJO0QBApMBTMUSy-CjmlOBX79auswEvQmdds-tqg-9ca_Gz7VSIrw5Y7_CsXanW1O0SF3Fajxfbbundd7fCqi33smmi4Ja2tVE6RyeVaoK9OMwRer-fvRWPyXzx8FRM54kRhHcJ5KCUFiVAqQ2UTGc6VSYDyq0QShuWp7SygpsKDADnClSeU6It45OMaGAjdLPfu_Hua2tDJ9d1MLZpVGvdNkhKgEGec8IiKvao8S4Ebyu58fVa-V2EZN9W9t1k300W0xdJQfZto3d1OLHVa1v-Wb8xI3B9AFQwqql8nyr8cyklTLCc_QCO6oJo</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>LEE, Jong-Ho</creator><creator>KIM, Ha-Neui</creator><creator>KIM, Kyung-Ok</creator><creator>WON JONG JIN</creator><creator>LEE, Seungbok</creator><creator>KIM, Hong-Hee</creator><creator>HYUNIL HA</creator><creator>ZANG HEE LEE</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120701</creationdate><title>CXCL10 Promotes Osteolytic Bone Metastasis by Enhancing Cancer Outgrowth and Osteoclastogenesis</title><author>LEE, Jong-Ho ; KIM, Ha-Neui ; KIM, Kyung-Ok ; WON JONG JIN ; LEE, Seungbok ; KIM, Hong-Hee ; HYUNIL HA ; ZANG HEE LEE</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-292aab5d22dbc2d3b8b6ac8214e55abc3961fe54cf2c2244a2a9910be34780b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Bone Neoplasms - secondary</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Chemokine CXCL10 - physiology</topic><topic>Diseases of the osteoarticular system</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Osteoclasts - pathology</topic><topic>Osteolysis</topic><topic>Pharmacology. 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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. 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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Antineoplastic agents Biological and medical sciences Bone Neoplasms - secondary Cell Differentiation - physiology Cell Line Cell Line, Tumor Chemokine CXCL10 - physiology Diseases of the osteoarticular system Enzyme-Linked Immunosorbent Assay Humans Medical sciences Mice Osteoclasts - pathology Osteolysis Pharmacology. Drug treatments Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Tumor Microenvironment Tumors Tumors of striated muscle and skeleton |
| title | CXCL10 Promotes Osteolytic Bone Metastasis by Enhancing Cancer Outgrowth and Osteoclastogenesis |
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