CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival
The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over‐expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL...
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| Veröffentlicht in: | The Journal of pathology 2015-02, Vol.235 (3), p.445-455 |
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| creator | Moreno, María José Bosch, Rosa Dieguez-Gonzalez, Rebeca Novelli, Silvana Mozos, Ana Gallardo, Alberto Pavón, Miguel Ángel Céspedes, María Virtudes Grañena, Albert Alcoceba, Miguel Blanco, Oscar Gonzalez-Díaz, Marcos Sierra, Jorge Mangues, Ramon Casanova, Isolda |
| description | The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over‐expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD/SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100, decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression‐free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd |
| doi_str_mv | 10.1002/path.4446 |
| format | Article |
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Over‐expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD/SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100, decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression‐free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.4446</identifier><identifier>PMID: 25231113</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; cell dissemination ; Cell Line, Tumor ; cell migration ; Cell Movement - physiology ; CXCR4 ; diffuse large B cell lymphoma ; Disease Models, Animal ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - physiology ; Heterocyclic Compounds - pharmacology ; Humans ; In Vitro Techniques ; Lymphoma, Large B-Cell, Diffuse - mortality ; Lymphoma, Large B-Cell, Diffuse - pathology ; Lymphoma, Large B-Cell, Diffuse - physiopathology ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasm Invasiveness - physiopathology ; Prognosis ; prognostic marker ; Receptors, CXCR4 - antagonists & inhibitors ; Receptors, CXCR4 - genetics ; Receptors, CXCR4 - physiology ; Survival Rate ; Xenograft Model Antitumor Assays</subject><ispartof>The Journal of pathology, 2015-02, Vol.235 (3), p.445-455</ispartof><rights>Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd</rights><rights>Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</rights><rights>Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5236-3442085e820541587fc7e4167d4d99b840b2db8a963d580c78df8502dfabad143</citedby><cites>FETCH-LOGICAL-c5236-3442085e820541587fc7e4167d4d99b840b2db8a963d580c78df8502dfabad143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.4446$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.4446$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25231113$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moreno, María José</creatorcontrib><creatorcontrib>Bosch, Rosa</creatorcontrib><creatorcontrib>Dieguez-Gonzalez, Rebeca</creatorcontrib><creatorcontrib>Novelli, Silvana</creatorcontrib><creatorcontrib>Mozos, Ana</creatorcontrib><creatorcontrib>Gallardo, Alberto</creatorcontrib><creatorcontrib>Pavón, Miguel Ángel</creatorcontrib><creatorcontrib>Céspedes, María Virtudes</creatorcontrib><creatorcontrib>Grañena, Albert</creatorcontrib><creatorcontrib>Alcoceba, Miguel</creatorcontrib><creatorcontrib>Blanco, Oscar</creatorcontrib><creatorcontrib>Gonzalez-Díaz, Marcos</creatorcontrib><creatorcontrib>Sierra, Jorge</creatorcontrib><creatorcontrib>Mangues, Ramon</creatorcontrib><creatorcontrib>Casanova, Isolda</creatorcontrib><title>CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over‐expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD/SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100, decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression‐free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd</description><subject>Animals</subject><subject>cell dissemination</subject><subject>Cell Line, Tumor</subject><subject>cell migration</subject><subject>Cell Movement - physiology</subject><subject>CXCR4</subject><subject>diffuse large B cell lymphoma</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Heterocyclic Compounds - pharmacology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Lymphoma, Large B-Cell, Diffuse - mortality</subject><subject>Lymphoma, Large B-Cell, Diffuse - pathology</subject><subject>Lymphoma, Large B-Cell, Diffuse - physiopathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness - physiopathology</subject><subject>Prognosis</subject><subject>prognostic marker</subject><subject>Receptors, CXCR4 - antagonists & inhibitors</subject><subject>Receptors, CXCR4 - genetics</subject><subject>Receptors, CXCR4 - physiology</subject><subject>Survival Rate</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1v1DAURS1ERactC_4AssQGFmltx3bsZYlgSqmgQkV0ZznxC-OSL-yk7fx7HM3QBRKrt3jnXh1dhF5RckoJYWejnTannHP5DK0o0TLTSsvnaJV-LMs5LQ7RUYx3hBCthXiBDplgOaU0XyFX3pbfOIbHMUCMfugx9Bvb1xCx800zR8CtDT8Bv8c1tC1ut924GTqbvjFC53s7LSHbO-ygDmBjSiYfD_2E4xzu_b1tT9BBY9sIL_f3GH3_-OGmvMiuvq4_ledXWZ18ZDLljCgBihHBqVBFUxfAqSwcd1pXipOKuUpZLXMnFKkL5RolCHONrayjPD9Gb3e9Yxh-zxAn0_m4aNsehjkaKgWXilPGEvrmH_RumEOf7BLFc6J0cknUux1VhyHGAI0Zg-9s2BpKzDK9WaY3y_SJfb1vnKsO3BP5d-sEnO2AB9_C9v9N5vr85mJfme0SPk7w-JSw4ZeRRV4I8-PL2ih2WfJ1cWs-538AEJycSA</recordid><startdate>201502</startdate><enddate>201502</enddate><creator>Moreno, María José</creator><creator>Bosch, Rosa</creator><creator>Dieguez-Gonzalez, Rebeca</creator><creator>Novelli, Silvana</creator><creator>Mozos, Ana</creator><creator>Gallardo, Alberto</creator><creator>Pavón, Miguel Ángel</creator><creator>Céspedes, María Virtudes</creator><creator>Grañena, Albert</creator><creator>Alcoceba, Miguel</creator><creator>Blanco, Oscar</creator><creator>Gonzalez-Díaz, Marcos</creator><creator>Sierra, Jorge</creator><creator>Mangues, Ramon</creator><creator>Casanova, Isolda</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201502</creationdate><title>CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival</title><author>Moreno, María José ; Bosch, Rosa ; Dieguez-Gonzalez, Rebeca ; Novelli, Silvana ; Mozos, Ana ; Gallardo, Alberto ; Pavón, Miguel Ángel ; Céspedes, María Virtudes ; Grañena, Albert ; Alcoceba, Miguel ; Blanco, Oscar ; Gonzalez-Díaz, Marcos ; Sierra, Jorge ; Mangues, Ramon ; Casanova, Isolda</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5236-3442085e820541587fc7e4167d4d99b840b2db8a963d580c78df8502dfabad143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>cell dissemination</topic><topic>Cell Line, Tumor</topic><topic>cell migration</topic><topic>Cell Movement - physiology</topic><topic>CXCR4</topic><topic>diffuse large B cell lymphoma</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Expression Regulation, Neoplastic - physiology</topic><topic>Heterocyclic Compounds - pharmacology</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Lymphoma, Large B-Cell, Diffuse - mortality</topic><topic>Lymphoma, Large B-Cell, Diffuse - pathology</topic><topic>Lymphoma, Large B-Cell, Diffuse - physiopathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness - physiopathology</topic><topic>Prognosis</topic><topic>prognostic marker</topic><topic>Receptors, CXCR4 - antagonists & inhibitors</topic><topic>Receptors, CXCR4 - genetics</topic><topic>Receptors, CXCR4 - physiology</topic><topic>Survival Rate</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moreno, María José</creatorcontrib><creatorcontrib>Bosch, Rosa</creatorcontrib><creatorcontrib>Dieguez-Gonzalez, Rebeca</creatorcontrib><creatorcontrib>Novelli, Silvana</creatorcontrib><creatorcontrib>Mozos, Ana</creatorcontrib><creatorcontrib>Gallardo, Alberto</creatorcontrib><creatorcontrib>Pavón, Miguel Ángel</creatorcontrib><creatorcontrib>Céspedes, María Virtudes</creatorcontrib><creatorcontrib>Grañena, Albert</creatorcontrib><creatorcontrib>Alcoceba, Miguel</creatorcontrib><creatorcontrib>Blanco, Oscar</creatorcontrib><creatorcontrib>Gonzalez-Díaz, Marcos</creatorcontrib><creatorcontrib>Sierra, Jorge</creatorcontrib><creatorcontrib>Mangues, Ramon</creatorcontrib><creatorcontrib>Casanova, Isolda</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moreno, María José</au><au>Bosch, Rosa</au><au>Dieguez-Gonzalez, Rebeca</au><au>Novelli, Silvana</au><au>Mozos, Ana</au><au>Gallardo, Alberto</au><au>Pavón, Miguel Ángel</au><au>Céspedes, María Virtudes</au><au>Grañena, Albert</au><au>Alcoceba, Miguel</au><au>Blanco, Oscar</au><au>Gonzalez-Díaz, Marcos</au><au>Sierra, Jorge</au><au>Mangues, Ramon</au><au>Casanova, Isolda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>2015-02</date><risdate>2015</risdate><volume>235</volume><issue>3</issue><spage>445</spage><epage>455</epage><pages>445-455</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><abstract>The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over‐expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD/SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100, decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression‐free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>25231113</pmid><doi>10.1002/path.4446</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals cell dissemination Cell Line, Tumor cell migration Cell Movement - physiology CXCR4 diffuse large B cell lymphoma Disease Models, Animal Disease Progression Female Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - physiology Heterocyclic Compounds - pharmacology Humans In Vitro Techniques Lymphoma, Large B-Cell, Diffuse - mortality Lymphoma, Large B-Cell, Diffuse - pathology Lymphoma, Large B-Cell, Diffuse - physiopathology Male Mice Mice, Inbred NOD Mice, SCID Middle Aged Neoplasm Invasiveness - physiopathology Prognosis prognostic marker Receptors, CXCR4 - antagonists & inhibitors Receptors, CXCR4 - genetics Receptors, CXCR4 - physiology Survival Rate Xenograft Model Antitumor Assays |
| title | CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival |
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