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Role of CXCL13-CXCR5 crosstalk between malignant neuroblastoma cells and Schwannian stromal cells in neuroblastic tumors
Neuroblastoma is a stroma-poor (SP) aggressive pediatric cancer belonging to neuroblastic tumors, also including ganglioneuroblastoma and ganglioneuroma, two stroma-rich (SR) less aggressive tumors. Our previous gene-expression profiling analysis showed a different CXCL13 mRNA expression between SP...
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| Published in: | Molecular cancer research 2011-07, Vol.9 (7), p.815-823 |
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| creator | Del Grosso, Federica Coco, Simona Scaruffi, Paola Stigliani, Sara Valdora, Francesca Benelli, Roberto Salvi, Sandra Boccardo, Simona Truini, Mauro Croce, Michela Ferrini, Silvano Longo, Luca Tonini, Gian Paolo |
| description | Neuroblastoma is a stroma-poor (SP) aggressive pediatric cancer belonging to neuroblastic tumors, also including ganglioneuroblastoma and ganglioneuroma, two stroma-rich (SR) less aggressive tumors. Our previous gene-expression profiling analysis showed a different CXCL13 mRNA expression between SP and SR tumors. Therefore, we studied 13 SP and 13 SR tumors by reverse transcription quantitative real-time PCR (RT-qPCR) and we found that CXCR5b was more expressed in SP than in SR and CXCL13 was predominantly expressed in SR tumors. Then, we isolated neuroblastic and Schwannian stromal cells by laser capture microdissection and we found that malignant neuroblasts express CXCR5b mRNA, whereas Schwannian stromal cells express CXCL13. Immunohistochemistry confirmed that stroma expresses CXCL13 but not CXCR5. To better understand the role of CXCL13 and CXCR5 in neuroblastic tumors we studied 11 neuroblastoma cell lines and we detected a heterogeneous expression of CXCL13 and CXCR5b. Interestingly, we found that only CXCR5b splice variant was expressed in both tumors and neuroblastoma lines, whereas CXCR5a was never detected. Moreover, we found that neuroblastoma cells expressing CXCR5 receptor migrate toward a source of recombinant CXCL13. Lastly, neuroblastoma cells induced to glial cell differentiation expressed CXCL13 mRNA and protein. The chemokine released in the culture medium was able to stimulate chemotaxis of LA1-5S neuroblastoma cells. Collectively, our data suggest that CXCL13 produced by stromal cells may contribute to the generation of an environment in which the malignant neuroblasts are retained, thus limiting the possible development of metastases in patients with SR tumor. |
| doi_str_mv | 10.1158/1541-7786.mcr-10-0367 |
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Our previous gene-expression profiling analysis showed a different CXCL13 mRNA expression between SP and SR tumors. Therefore, we studied 13 SP and 13 SR tumors by reverse transcription quantitative real-time PCR (RT-qPCR) and we found that CXCR5b was more expressed in SP than in SR and CXCL13 was predominantly expressed in SR tumors. Then, we isolated neuroblastic and Schwannian stromal cells by laser capture microdissection and we found that malignant neuroblasts express CXCR5b mRNA, whereas Schwannian stromal cells express CXCL13. Immunohistochemistry confirmed that stroma expresses CXCL13 but not CXCR5. To better understand the role of CXCL13 and CXCR5 in neuroblastic tumors we studied 11 neuroblastoma cell lines and we detected a heterogeneous expression of CXCL13 and CXCR5b. Interestingly, we found that only CXCR5b splice variant was expressed in both tumors and neuroblastoma lines, whereas CXCR5a was never detected. Moreover, we found that neuroblastoma cells expressing CXCR5 receptor migrate toward a source of recombinant CXCL13. Lastly, neuroblastoma cells induced to glial cell differentiation expressed CXCL13 mRNA and protein. The chemokine released in the culture medium was able to stimulate chemotaxis of LA1-5S neuroblastoma cells. Collectively, our data suggest that CXCL13 produced by stromal cells may contribute to the generation of an environment in which the malignant neuroblasts are retained, thus limiting the possible development of metastases in patients with SR tumor.</description><identifier>ISSN: 1541-7786</identifier><identifier>EISSN: 1557-3125</identifier><identifier>DOI: 10.1158/1541-7786.mcr-10-0367</identifier><identifier>PMID: 21642390</identifier><language>eng</language><publisher>United States</publisher><subject>Alternative splicing ; Cancer ; Cell culture ; Cell Differentiation ; Cell Line, Tumor ; Cell migration ; Cell Movement ; Chemokine CXCL13 - genetics ; Chemokine CXCL13 - metabolism ; Chemotaxis ; Child ; CXCL13 protein ; CXCR5 protein ; Differentiation ; Gene expression ; Gene Expression Profiling ; Humans ; Lasers ; Neuroblastoma ; Neuroblastoma - metabolism ; Neuroblastoma - pathology ; Neuroblastoma cells ; Neuroblasts ; Pediatrics ; Polymerase chain reaction ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Receptors, CXCR5 - genetics ; Receptors, CXCR5 - metabolism ; Reverse transcription ; Schwann Cells - metabolism ; Schwann Cells - pathology ; stromal cells ; Stromal Cells - metabolism ; Stromal Cells - pathology ; Substance P ; Tumors</subject><ispartof>Molecular cancer research, 2011-07, Vol.9 (7), p.815-823</ispartof><rights>2011 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-5b12da61d75b29e798ebf85d59d0db9e17890152019a32af5cf9f1fad0681e3b3</citedby><cites>FETCH-LOGICAL-c454t-5b12da61d75b29e798ebf85d59d0db9e17890152019a32af5cf9f1fad0681e3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21642390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Del Grosso, Federica</creatorcontrib><creatorcontrib>Coco, Simona</creatorcontrib><creatorcontrib>Scaruffi, Paola</creatorcontrib><creatorcontrib>Stigliani, Sara</creatorcontrib><creatorcontrib>Valdora, Francesca</creatorcontrib><creatorcontrib>Benelli, Roberto</creatorcontrib><creatorcontrib>Salvi, Sandra</creatorcontrib><creatorcontrib>Boccardo, Simona</creatorcontrib><creatorcontrib>Truini, Mauro</creatorcontrib><creatorcontrib>Croce, Michela</creatorcontrib><creatorcontrib>Ferrini, Silvano</creatorcontrib><creatorcontrib>Longo, Luca</creatorcontrib><creatorcontrib>Tonini, Gian Paolo</creatorcontrib><title>Role of CXCL13-CXCR5 crosstalk between malignant neuroblastoma cells and Schwannian stromal cells in neuroblastic tumors</title><title>Molecular cancer research</title><addtitle>Mol Cancer Res</addtitle><description>Neuroblastoma is a stroma-poor (SP) aggressive pediatric cancer belonging to neuroblastic tumors, also including ganglioneuroblastoma and ganglioneuroma, two stroma-rich (SR) less aggressive tumors. Our previous gene-expression profiling analysis showed a different CXCL13 mRNA expression between SP and SR tumors. Therefore, we studied 13 SP and 13 SR tumors by reverse transcription quantitative real-time PCR (RT-qPCR) and we found that CXCR5b was more expressed in SP than in SR and CXCL13 was predominantly expressed in SR tumors. Then, we isolated neuroblastic and Schwannian stromal cells by laser capture microdissection and we found that malignant neuroblasts express CXCR5b mRNA, whereas Schwannian stromal cells express CXCL13. Immunohistochemistry confirmed that stroma expresses CXCL13 but not CXCR5. To better understand the role of CXCL13 and CXCR5 in neuroblastic tumors we studied 11 neuroblastoma cell lines and we detected a heterogeneous expression of CXCL13 and CXCR5b. Interestingly, we found that only CXCR5b splice variant was expressed in both tumors and neuroblastoma lines, whereas CXCR5a was never detected. Moreover, we found that neuroblastoma cells expressing CXCR5 receptor migrate toward a source of recombinant CXCL13. Lastly, neuroblastoma cells induced to glial cell differentiation expressed CXCL13 mRNA and protein. The chemokine released in the culture medium was able to stimulate chemotaxis of LA1-5S neuroblastoma cells. Collectively, our data suggest that CXCL13 produced by stromal cells may contribute to the generation of an environment in which the malignant neuroblasts are retained, thus limiting the possible development of metastases in patients with SR tumor.</description><subject>Alternative splicing</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell Differentiation</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Chemokine CXCL13 - genetics</subject><subject>Chemokine CXCL13 - metabolism</subject><subject>Chemotaxis</subject><subject>Child</subject><subject>CXCL13 protein</subject><subject>CXCR5 protein</subject><subject>Differentiation</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Lasers</subject><subject>Neuroblastoma</subject><subject>Neuroblastoma - metabolism</subject><subject>Neuroblastoma - pathology</subject><subject>Neuroblastoma cells</subject><subject>Neuroblasts</subject><subject>Pediatrics</subject><subject>Polymerase chain reaction</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Receptors, CXCR5 - genetics</subject><subject>Receptors, CXCR5 - metabolism</subject><subject>Reverse transcription</subject><subject>Schwann Cells - metabolism</subject><subject>Schwann Cells - pathology</subject><subject>stromal cells</subject><subject>Stromal Cells - metabolism</subject><subject>Stromal Cells - pathology</subject><subject>Substance P</subject><subject>Tumors</subject><issn>1541-7786</issn><issn>1557-3125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp9UctOwzAQtBCIQuETQL7BJcUbx7F9RBEvqQipgMQtshMbAolT7ESFvyehBXHitKvdmX3MIHQEZAbAxBmwBCLORTprCh8BiQhN-RbaA8Z4RCFm22O-wUzQfgivhMQEeLqLJjGkSUwl2UMfi7Y2uLU4e8rmQKMhLBgufBtCp-o3rE23MsbhRtXVs1Ouw870vtW1Cl3bKFyYug5YuRLfFy8r5VylHA6dH3r1plm5P5yqwF3ftD4coB2r6mAON3GKHi8vHrLraH53dZOdz6MiYUkXMQ1xqVIoOdOxNFwKo61gJZMlKbU0wIUkwIbHpKKxsqyw0oJVJUkFGKrpFJ2s5y59-96b0OVNFcbDlDNtH3LBBZOMDnJM0em_SAAOIqUxyAHK1tBvobyx-dJXjfKfOZB8tCcfpc9H6fPbbDFWR3sG3vFmRa8bU_6yfvygX12AjKc</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Del Grosso, Federica</creator><creator>Coco, Simona</creator><creator>Scaruffi, Paola</creator><creator>Stigliani, Sara</creator><creator>Valdora, Francesca</creator><creator>Benelli, Roberto</creator><creator>Salvi, Sandra</creator><creator>Boccardo, Simona</creator><creator>Truini, Mauro</creator><creator>Croce, Michela</creator><creator>Ferrini, Silvano</creator><creator>Longo, Luca</creator><creator>Tonini, Gian Paolo</creator><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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20110701</creationdate><title>Role of CXCL13-CXCR5 crosstalk between malignant neuroblastoma cells and Schwannian stromal cells in neuroblastic tumors</title><author>Del Grosso, Federica ; Coco, Simona ; Scaruffi, Paola ; Stigliani, Sara ; Valdora, Francesca ; Benelli, Roberto ; Salvi, Sandra ; Boccardo, Simona ; Truini, Mauro ; Croce, Michela ; Ferrini, Silvano ; Longo, Luca ; Tonini, Gian Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-5b12da61d75b29e798ebf85d59d0db9e17890152019a32af5cf9f1fad0681e3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alternative splicing</topic><topic>Cancer</topic><topic>Cell culture</topic><topic>Cell Differentiation</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Chemokine CXCL13 - genetics</topic><topic>Chemokine CXCL13 - metabolism</topic><topic>Chemotaxis</topic><topic>Child</topic><topic>CXCL13 protein</topic><topic>CXCR5 protein</topic><topic>Differentiation</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Lasers</topic><topic>Neuroblastoma</topic><topic>Neuroblastoma - metabolism</topic><topic>Neuroblastoma - pathology</topic><topic>Neuroblastoma cells</topic><topic>Neuroblasts</topic><topic>Pediatrics</topic><topic>Polymerase chain reaction</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Receptors, CXCR5 - genetics</topic><topic>Receptors, CXCR5 - metabolism</topic><topic>Reverse transcription</topic><topic>Schwann Cells - metabolism</topic><topic>Schwann Cells - pathology</topic><topic>stromal cells</topic><topic>Stromal Cells - metabolism</topic><topic>Stromal Cells - pathology</topic><topic>Substance P</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Del Grosso, Federica</creatorcontrib><creatorcontrib>Coco, Simona</creatorcontrib><creatorcontrib>Scaruffi, Paola</creatorcontrib><creatorcontrib>Stigliani, Sara</creatorcontrib><creatorcontrib>Valdora, Francesca</creatorcontrib><creatorcontrib>Benelli, Roberto</creatorcontrib><creatorcontrib>Salvi, Sandra</creatorcontrib><creatorcontrib>Boccardo, Simona</creatorcontrib><creatorcontrib>Truini, Mauro</creatorcontrib><creatorcontrib>Croce, Michela</creatorcontrib><creatorcontrib>Ferrini, Silvano</creatorcontrib><creatorcontrib>Longo, Luca</creatorcontrib><creatorcontrib>Tonini, Gian Paolo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Del Grosso, Federica</au><au>Coco, Simona</au><au>Scaruffi, Paola</au><au>Stigliani, Sara</au><au>Valdora, Francesca</au><au>Benelli, Roberto</au><au>Salvi, Sandra</au><au>Boccardo, Simona</au><au>Truini, Mauro</au><au>Croce, Michela</au><au>Ferrini, Silvano</au><au>Longo, Luca</au><au>Tonini, Gian Paolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of CXCL13-CXCR5 crosstalk between malignant neuroblastoma cells and Schwannian stromal cells in neuroblastic tumors</atitle><jtitle>Molecular cancer research</jtitle><addtitle>Mol Cancer Res</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>9</volume><issue>7</issue><spage>815</spage><epage>823</epage><pages>815-823</pages><issn>1541-7786</issn><eissn>1557-3125</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><abstract>Neuroblastoma is a stroma-poor (SP) aggressive pediatric cancer belonging to neuroblastic tumors, also including ganglioneuroblastoma and ganglioneuroma, two stroma-rich (SR) less aggressive tumors. Our previous gene-expression profiling analysis showed a different CXCL13 mRNA expression between SP and SR tumors. Therefore, we studied 13 SP and 13 SR tumors by reverse transcription quantitative real-time PCR (RT-qPCR) and we found that CXCR5b was more expressed in SP than in SR and CXCL13 was predominantly expressed in SR tumors. Then, we isolated neuroblastic and Schwannian stromal cells by laser capture microdissection and we found that malignant neuroblasts express CXCR5b mRNA, whereas Schwannian stromal cells express CXCL13. Immunohistochemistry confirmed that stroma expresses CXCL13 but not CXCR5. To better understand the role of CXCL13 and CXCR5 in neuroblastic tumors we studied 11 neuroblastoma cell lines and we detected a heterogeneous expression of CXCL13 and CXCR5b. Interestingly, we found that only CXCR5b splice variant was expressed in both tumors and neuroblastoma lines, whereas CXCR5a was never detected. Moreover, we found that neuroblastoma cells expressing CXCR5 receptor migrate toward a source of recombinant CXCL13. Lastly, neuroblastoma cells induced to glial cell differentiation expressed CXCL13 mRNA and protein. The chemokine released in the culture medium was able to stimulate chemotaxis of LA1-5S neuroblastoma cells. Collectively, our data suggest that CXCL13 produced by stromal cells may contribute to the generation of an environment in which the malignant neuroblasts are retained, thus limiting the possible development of metastases in patients with SR tumor.</abstract><cop>United States</cop><pmid>21642390</pmid><doi>10.1158/1541-7786.mcr-10-0367</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alternative splicing Cancer Cell culture Cell Differentiation Cell Line, Tumor Cell migration Cell Movement Chemokine CXCL13 - genetics Chemokine CXCL13 - metabolism Chemotaxis Child CXCL13 protein CXCR5 protein Differentiation Gene expression Gene Expression Profiling Humans Lasers Neuroblastoma Neuroblastoma - metabolism Neuroblastoma - pathology Neuroblastoma cells Neuroblasts Pediatrics Polymerase chain reaction Protein Isoforms - genetics Protein Isoforms - metabolism Receptors, CXCR5 - genetics Receptors, CXCR5 - metabolism Reverse transcription Schwann Cells - metabolism Schwann Cells - pathology stromal cells Stromal Cells - metabolism Stromal Cells - pathology Substance P Tumors |
| title | Role of CXCL13-CXCR5 crosstalk between malignant neuroblastoma cells and Schwannian stromal cells in neuroblastic tumors |
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