Angiostatic and chemotactic activities of the CXC chemokine CXCL4L1 (platelet factor-4 variant) are mediated by CXCR3
We investigated possible cellular receptors for the human CXC chemokine platelet factor-4 variant/CXCL4L1, a potent inhibitor of angiogenesis. We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displa...
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| Veröffentlicht in: | Blood 2011-01, Vol.117 (2), p.480-488 |
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| creator | Struyf, Sofie Salogni, Laura Burdick, Marie D. Vandercappellen, Jo Gouwy, Mieke Noppen, Sam Proost, Paul Opdenakker, Ghislain Parmentier, Marc Gerard, Craig Sozzani, Silvano Strieter, Robert M. Van Damme, Jo |
| description | We investigated possible cellular receptors for the human CXC chemokine platelet factor-4 variant/CXCL4L1, a potent inhibitor of angiogenesis. We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displace each other on microvascular endothelial cells. Labeled CXCL4L1 also bound to CXCR3A- and CXCR3B-transfectants and was displaced by CXCL4L1, CXCL4, and CXCL10. The CXCL4L1 anti-angiogenic activity was blocked by anti-CXCR3 antibodies (Abs) in the Matrigel and cornea micropocket assays. CXCL4L1 application in CXCR3−/− or in wild-type mice treated with neutralizing anti-CXCR3 Abs, resulted in reduced inhibitory activity of CXCL4L1 on tumor growth and vascularization of Lewis lung carcinoma. Furthermore, CXCL4L1 and CXCL4 chemoattracted activated T cells, human natural killer cells, and human immature dendritic cells (DCs). Migration of DCs toward CXCL4 and CXCL4L1 was desensitized by preincubation with CXCL10 and CXCL11, inhibited by pertussis toxin, and neutralized by anti-CXCR3 Abs. Chemotaxis of T cells, natural killer cells, and DCs is likely to contribute to the antitumoral action. However, the in vivo data indicate that the angiostatic property of CXCL4L1 is equally important in retarding tumor growth. Thus, both CXCR3A and CXCR3B are implicated in the chemotactic and vascular effects of CXCL4L1. |
| doi_str_mv | 10.1182/blood-2009-11-253591 |
| format | Article |
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We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displace each other on microvascular endothelial cells. Labeled CXCL4L1 also bound to CXCR3A- and CXCR3B-transfectants and was displaced by CXCL4L1, CXCL4, and CXCL10. The CXCL4L1 anti-angiogenic activity was blocked by anti-CXCR3 antibodies (Abs) in the Matrigel and cornea micropocket assays. CXCL4L1 application in CXCR3−/− or in wild-type mice treated with neutralizing anti-CXCR3 Abs, resulted in reduced inhibitory activity of CXCL4L1 on tumor growth and vascularization of Lewis lung carcinoma. Furthermore, CXCL4L1 and CXCL4 chemoattracted activated T cells, human natural killer cells, and human immature dendritic cells (DCs). Migration of DCs toward CXCL4 and CXCL4L1 was desensitized by preincubation with CXCL10 and CXCL11, inhibited by pertussis toxin, and neutralized by anti-CXCR3 Abs. Chemotaxis of T cells, natural killer cells, and DCs is likely to contribute to the antitumoral action. However, the in vivo data indicate that the angiostatic property of CXCL4L1 is equally important in retarding tumor growth. Thus, both CXCR3A and CXCR3B are implicated in the chemotactic and vascular effects of CXCL4L1.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2009-11-253591</identifier><identifier>PMID: 20980681</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Angiogenesis Inhibitors - metabolism ; Angiogenesis Inhibitors - pharmacology ; Animals ; Antineoplastic Agents - metabolism ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Chemotactic Factors - metabolism ; Chemotactic Factors - pharmacology ; Chemotaxis, Leukocyte - drug effects ; Chemotaxis, Leukocyte - physiology ; Dendritic Cells - metabolism ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Hematologic and hematopoietic diseases ; Humans ; Immunobiology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - metabolism ; Platelet Factor 4 - metabolism ; Platelet Factor 4 - pharmacology ; Rats ; Receptors, CXCR3 - metabolism ; Transfection ; Xenograft Model Antitumor Assays</subject><ispartof>Blood, 2011-01, Vol.117 (2), p.480-488</ispartof><rights>2011 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><rights>2011 by The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c558t-2750e4941f78175632680ab4e8a4e9ecf59e01fec06cc04a8c6a39dd9b7bf7a33</citedby><cites>FETCH-LOGICAL-c558t-2750e4941f78175632680ab4e8a4e9ecf59e01fec06cc04a8c6a39dd9b7bf7a33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23744062$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20980681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Struyf, Sofie</creatorcontrib><creatorcontrib>Salogni, Laura</creatorcontrib><creatorcontrib>Burdick, Marie D.</creatorcontrib><creatorcontrib>Vandercappellen, Jo</creatorcontrib><creatorcontrib>Gouwy, Mieke</creatorcontrib><creatorcontrib>Noppen, Sam</creatorcontrib><creatorcontrib>Proost, Paul</creatorcontrib><creatorcontrib>Opdenakker, Ghislain</creatorcontrib><creatorcontrib>Parmentier, Marc</creatorcontrib><creatorcontrib>Gerard, Craig</creatorcontrib><creatorcontrib>Sozzani, Silvano</creatorcontrib><creatorcontrib>Strieter, Robert M.</creatorcontrib><creatorcontrib>Van Damme, Jo</creatorcontrib><title>Angiostatic and chemotactic activities of the CXC chemokine CXCL4L1 (platelet factor-4 variant) are mediated by CXCR3</title><title>Blood</title><addtitle>Blood</addtitle><description>We investigated possible cellular receptors for the human CXC chemokine platelet factor-4 variant/CXCL4L1, a potent inhibitor of angiogenesis. We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displace each other on microvascular endothelial cells. Labeled CXCL4L1 also bound to CXCR3A- and CXCR3B-transfectants and was displaced by CXCL4L1, CXCL4, and CXCL10. The CXCL4L1 anti-angiogenic activity was blocked by anti-CXCR3 antibodies (Abs) in the Matrigel and cornea micropocket assays. CXCL4L1 application in CXCR3−/− or in wild-type mice treated with neutralizing anti-CXCR3 Abs, resulted in reduced inhibitory activity of CXCL4L1 on tumor growth and vascularization of Lewis lung carcinoma. Furthermore, CXCL4L1 and CXCL4 chemoattracted activated T cells, human natural killer cells, and human immature dendritic cells (DCs). Migration of DCs toward CXCL4 and CXCL4L1 was desensitized by preincubation with CXCL10 and CXCL11, inhibited by pertussis toxin, and neutralized by anti-CXCR3 Abs. Chemotaxis of T cells, natural killer cells, and DCs is likely to contribute to the antitumoral action. However, the in vivo data indicate that the angiostatic property of CXCL4L1 is equally important in retarding tumor growth. Thus, both CXCR3A and CXCR3B are implicated in the chemotactic and vascular effects of CXCL4L1.</description><subject>Angiogenesis Inhibitors - metabolism</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Chemotactic Factors - metabolism</subject><subject>Chemotactic Factors - pharmacology</subject><subject>Chemotaxis, Leukocyte - drug effects</subject><subject>Chemotaxis, Leukocyte - physiology</subject><subject>Dendritic Cells - metabolism</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Platelet Factor 4 - metabolism</subject><subject>Platelet Factor 4 - pharmacology</subject><subject>Rats</subject><subject>Receptors, CXCR3 - metabolism</subject><subject>Transfection</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kVuLFDEQhYMo7rj6D0TyIupDa-XWnbwIy-ANBgRR8C2k09U70Z7OmGQG9t-bubirL74kFPlO1UkdQp4yeM2Y5m_6Kcah4QCmYazhSijD7pEFU1w3ABzukwUAtI00Hbsgj3L-AcCk4OohueBgNLSaLcjuar4OMRdXgqduHqhf4yYW5491PfehBMw0jrSskS6_L0_EzzAfq5VcMfpyO7mCExY6VklMjaR7l4KbyyvqEtINDqECA-1vDpov4jF5MLop45PzfUm-vX_3dfmxWX3-8Gl5tWq8Uro0vFOA0kg2dpp1qhW81eB6idpJNOhHZRDYiB5a70E67VsnzDCYvuvHzglxSd6e-m53fTXhcS7JTXabwsalGxtdsP--zGFtr-PeChBMdl1t8OLcIMVfO8zFbkL2OE1uxrjLVksQignDKilPpE8x54Tj7RQG9hCYPQZmD4HV2p4Cq7Jnfzu8Ff1JqALPz4DL3k1jcrMP-Y4TnZTQ8ruvYt3nPmCy2QecfV19Ql_sEMP_nfwGZea0wA</recordid><startdate>20110113</startdate><enddate>20110113</enddate><creator>Struyf, Sofie</creator><creator>Salogni, Laura</creator><creator>Burdick, Marie D.</creator><creator>Vandercappellen, Jo</creator><creator>Gouwy, Mieke</creator><creator>Noppen, Sam</creator><creator>Proost, Paul</creator><creator>Opdenakker, Ghislain</creator><creator>Parmentier, Marc</creator><creator>Gerard, Craig</creator><creator>Sozzani, Silvano</creator><creator>Strieter, Robert M.</creator><creator>Van Damme, Jo</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><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><scope>5PM</scope></search><sort><creationdate>20110113</creationdate><title>Angiostatic and chemotactic activities of the CXC chemokine CXCL4L1 (platelet factor-4 variant) are mediated by CXCR3</title><author>Struyf, Sofie ; Salogni, Laura ; Burdick, Marie D. ; Vandercappellen, Jo ; Gouwy, Mieke ; Noppen, Sam ; Proost, Paul ; Opdenakker, Ghislain ; Parmentier, Marc ; Gerard, Craig ; Sozzani, Silvano ; Strieter, Robert M. ; Van Damme, Jo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c558t-2750e4941f78175632680ab4e8a4e9ecf59e01fec06cc04a8c6a39dd9b7bf7a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Angiogenesis Inhibitors - metabolism</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Chemotactic Factors - metabolism</topic><topic>Chemotactic Factors - pharmacology</topic><topic>Chemotaxis, Leukocyte - drug effects</topic><topic>Chemotaxis, Leukocyte - physiology</topic><topic>Dendritic Cells - metabolism</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Platelet Factor 4 - metabolism</topic><topic>Platelet Factor 4 - pharmacology</topic><topic>Rats</topic><topic>Receptors, CXCR3 - metabolism</topic><topic>Transfection</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Struyf, Sofie</creatorcontrib><creatorcontrib>Salogni, Laura</creatorcontrib><creatorcontrib>Burdick, Marie D.</creatorcontrib><creatorcontrib>Vandercappellen, Jo</creatorcontrib><creatorcontrib>Gouwy, Mieke</creatorcontrib><creatorcontrib>Noppen, Sam</creatorcontrib><creatorcontrib>Proost, Paul</creatorcontrib><creatorcontrib>Opdenakker, Ghislain</creatorcontrib><creatorcontrib>Parmentier, Marc</creatorcontrib><creatorcontrib>Gerard, Craig</creatorcontrib><creatorcontrib>Sozzani, Silvano</creatorcontrib><creatorcontrib>Strieter, Robert M.</creatorcontrib><creatorcontrib>Van Damme, Jo</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Struyf, Sofie</au><au>Salogni, Laura</au><au>Burdick, Marie D.</au><au>Vandercappellen, Jo</au><au>Gouwy, Mieke</au><au>Noppen, Sam</au><au>Proost, Paul</au><au>Opdenakker, Ghislain</au><au>Parmentier, Marc</au><au>Gerard, Craig</au><au>Sozzani, Silvano</au><au>Strieter, Robert M.</au><au>Van Damme, Jo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiostatic and chemotactic activities of the CXC chemokine CXCL4L1 (platelet factor-4 variant) are mediated by CXCR3</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2011-01-13</date><risdate>2011</risdate><volume>117</volume><issue>2</issue><spage>480</spage><epage>488</epage><pages>480-488</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>We investigated possible cellular receptors for the human CXC chemokine platelet factor-4 variant/CXCL4L1, a potent inhibitor of angiogenesis. We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displace each other on microvascular endothelial cells. Labeled CXCL4L1 also bound to CXCR3A- and CXCR3B-transfectants and was displaced by CXCL4L1, CXCL4, and CXCL10. The CXCL4L1 anti-angiogenic activity was blocked by anti-CXCR3 antibodies (Abs) in the Matrigel and cornea micropocket assays. CXCL4L1 application in CXCR3−/− or in wild-type mice treated with neutralizing anti-CXCR3 Abs, resulted in reduced inhibitory activity of CXCL4L1 on tumor growth and vascularization of Lewis lung carcinoma. Furthermore, CXCL4L1 and CXCL4 chemoattracted activated T cells, human natural killer cells, and human immature dendritic cells (DCs). Migration of DCs toward CXCL4 and CXCL4L1 was desensitized by preincubation with CXCL10 and CXCL11, inhibited by pertussis toxin, and neutralized by anti-CXCR3 Abs. Chemotaxis of T cells, natural killer cells, and DCs is likely to contribute to the antitumoral action. However, the in vivo data indicate that the angiostatic property of CXCL4L1 is equally important in retarding tumor growth. Thus, both CXCR3A and CXCR3B are implicated in the chemotactic and vascular effects of CXCL4L1.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>20980681</pmid><doi>10.1182/blood-2009-11-253591</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Blood, 2011-01, Vol.117 (2), p.480-488 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Angiogenesis Inhibitors - metabolism Angiogenesis Inhibitors - pharmacology Animals Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology Biological and medical sciences Chemotactic Factors - metabolism Chemotactic Factors - pharmacology Chemotaxis, Leukocyte - drug effects Chemotaxis, Leukocyte - physiology Dendritic Cells - metabolism Endothelial Cells - drug effects Endothelial Cells - metabolism Hematologic and hematopoietic diseases Humans Immunobiology Medical sciences Mice Mice, Inbred C57BL Neoplasms, Experimental - drug therapy Neoplasms, Experimental - metabolism Platelet Factor 4 - metabolism Platelet Factor 4 - pharmacology Rats Receptors, CXCR3 - metabolism Transfection Xenograft Model Antitumor Assays |
| title | Angiostatic and chemotactic activities of the CXC chemokine CXCL4L1 (platelet factor-4 variant) are mediated by CXCR3 |
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