Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
Myeloma cell adhesion dependent on α4β1 integrin is crucial for the progression of multiple myeloma (MM). The α4β1‐dependent myeloma cell adhesion is up‐regulated by the chemokine CXCL12, and pharmacological blockade of the CXCL12 receptor CXCR4 leads to defective myeloma cell homing to bone marrow...
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| Veröffentlicht in: | The Journal of pathology 2013-01, Vol.229 (1), p.36-48 |
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| creator | García-Bernal, David Redondo-Muñoz, Javier Dios-Esponera, Ana Chèvre, Raphaël Bailón, Elvira Garayoa, Mercedes Arellano-Sánchez, Nohemí Gutierrez, Norma C Hidalgo, Andrés García-Pardo, Angeles Teixidó, Joaquin |
| description | Myeloma cell adhesion dependent on α4β1 integrin is crucial for the progression of multiple myeloma (MM). The α4β1‐dependent myeloma cell adhesion is up‐regulated by the chemokine CXCL12, and pharmacological blockade of the CXCL12 receptor CXCR4 leads to defective myeloma cell homing to bone marrow (BM). Sphingosine‐1‐phosphate (S1P) regulates immune cell trafficking upon binding to G‐protein‐coupled receptors. Here we show that myeloma cells express S1P1, a receptor for S1P. We found that S1P up‐regulated the α4β1‐mediated myeloma cell adhesion and transendothelial migration stimulated by CXCL12. S1P promoted generation of high‐affinity α4β1 that efficiently bound the α4β1 ligand VCAM‐1, a finding that was associated with S1P‐triggered increase in talin‐β1 integrin association. Furthermore, S1P cooperated with CXCL12 for enhancement of α4β1‐dependent adhesion strengthening and spreading. CXCL12 and S1P activated the DOCK2‐Rac1 pathway, which was required for stimulation of myeloma cell adhesion involving α4β1. Moreover, in vivo analyses indicated that S1P contributes to optimizing the interactions of MM cells with the BM microvasculture and for their lodging inside the bone marrow. The regulation of α4β1‐dependent adhesion and migration of myeloma cells by CXCL12‐S1P combined activities might have important consequences for myeloma disease progression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/path.4066 |
| format | Article |
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The α4β1‐dependent myeloma cell adhesion is up‐regulated by the chemokine CXCL12, and pharmacological blockade of the CXCL12 receptor CXCR4 leads to defective myeloma cell homing to bone marrow (BM). Sphingosine‐1‐phosphate (S1P) regulates immune cell trafficking upon binding to G‐protein‐coupled receptors. Here we show that myeloma cells express S1P1, a receptor for S1P. We found that S1P up‐regulated the α4β1‐mediated myeloma cell adhesion and transendothelial migration stimulated by CXCL12. S1P promoted generation of high‐affinity α4β1 that efficiently bound the α4β1 ligand VCAM‐1, a finding that was associated with S1P‐triggered increase in talin‐β1 integrin association. Furthermore, S1P cooperated with CXCL12 for enhancement of α4β1‐dependent adhesion strengthening and spreading. CXCL12 and S1P activated the DOCK2‐Rac1 pathway, which was required for stimulation of myeloma cell adhesion involving α4β1. Moreover, in vivo analyses indicated that S1P contributes to optimizing the interactions of MM cells with the BM microvasculture and for their lodging inside the bone marrow. The regulation of α4β1‐dependent adhesion and migration of myeloma cells by CXCL12‐S1P combined activities might have important consequences for myeloma disease progression. Copyright © 2012 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.4066</identifier><identifier>PMID: 22711564</identifier><identifier>CODEN: JPTLAS</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Biological and medical sciences ; bone marrow ; Bone Marrow - blood supply ; Bone Marrow - immunology ; Bone Marrow - metabolism ; Bone Marrow - pathology ; Cell Adhesion ; cell adhesion and migration ; Cell Shape ; Chemokine CXCL12 - metabolism ; chemokines ; Coculture Techniques ; Guanine Nucleotide Exchange Factors - metabolism ; Hematologic and hematopoietic diseases ; Humans ; Immunodeficiencies. Immunoglobulinopathies ; Immunoglobulinopathies ; Immunopathology ; Integrin alpha4beta1 - metabolism ; Integrin alpha5beta1 - metabolism ; integrins ; Investigative techniques, diagnostic techniques (general aspects) ; K562 Cells ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lysophospholipids - metabolism ; Medical sciences ; Mice ; Mice, Inbred NOD ; Mice, SCID ; multiple myeloma ; Multiple Myeloma - genetics ; Multiple Myeloma - immunology ; Multiple Myeloma - metabolism ; Multiple Myeloma - pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; rac1 GTP-Binding Protein - metabolism ; Receptors, Lysosphingolipid - genetics ; Receptors, Lysosphingolipid - metabolism ; RNA Interference ; Signal Transduction ; signalling ; Sphingosine - analogs & derivatives ; Sphingosine - metabolism ; Stromal Cells - immunology ; Stromal Cells - metabolism ; Stromal Cells - pathology ; Talin - metabolism ; Time Factors ; Transendothelial and Transepithelial Migration ; Transfection ; Tumor Cells, Cultured ; Vascular Cell Adhesion Molecule-1 - metabolism</subject><ispartof>The Journal of pathology, 2013-01, Vol.229 (1), p.36-48</ispartof><rights>Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4616-25d40441f40de60a4301c4af0c6274089c5e69627ff0bf32379b29ad5733ab533</citedby><cites>FETCH-LOGICAL-c4616-25d40441f40de60a4301c4af0c6274089c5e69627ff0bf32379b29ad5733ab533</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.4066$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.4066$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26756731$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22711564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>García-Bernal, David</creatorcontrib><creatorcontrib>Redondo-Muñoz, Javier</creatorcontrib><creatorcontrib>Dios-Esponera, Ana</creatorcontrib><creatorcontrib>Chèvre, Raphaël</creatorcontrib><creatorcontrib>Bailón, Elvira</creatorcontrib><creatorcontrib>Garayoa, Mercedes</creatorcontrib><creatorcontrib>Arellano-Sánchez, Nohemí</creatorcontrib><creatorcontrib>Gutierrez, Norma C</creatorcontrib><creatorcontrib>Hidalgo, Andrés</creatorcontrib><creatorcontrib>García-Pardo, Angeles</creatorcontrib><creatorcontrib>Teixidó, Joaquin</creatorcontrib><title>Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>Myeloma cell adhesion dependent on α4β1 integrin is crucial for the progression of multiple myeloma (MM). The α4β1‐dependent myeloma cell adhesion is up‐regulated by the chemokine CXCL12, and pharmacological blockade of the CXCL12 receptor CXCR4 leads to defective myeloma cell homing to bone marrow (BM). Sphingosine‐1‐phosphate (S1P) regulates immune cell trafficking upon binding to G‐protein‐coupled receptors. Here we show that myeloma cells express S1P1, a receptor for S1P. We found that S1P up‐regulated the α4β1‐mediated myeloma cell adhesion and transendothelial migration stimulated by CXCL12. S1P promoted generation of high‐affinity α4β1 that efficiently bound the α4β1 ligand VCAM‐1, a finding that was associated with S1P‐triggered increase in talin‐β1 integrin association. Furthermore, S1P cooperated with CXCL12 for enhancement of α4β1‐dependent adhesion strengthening and spreading. CXCL12 and S1P activated the DOCK2‐Rac1 pathway, which was required for stimulation of myeloma cell adhesion involving α4β1. Moreover, in vivo analyses indicated that S1P contributes to optimizing the interactions of MM cells with the BM microvasculture and for their lodging inside the bone marrow. The regulation of α4β1‐dependent adhesion and migration of myeloma cells by CXCL12‐S1P combined activities might have important consequences for myeloma disease progression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>bone marrow</subject><subject>Bone Marrow - blood supply</subject><subject>Bone Marrow - immunology</subject><subject>Bone Marrow - metabolism</subject><subject>Bone Marrow - pathology</subject><subject>Cell Adhesion</subject><subject>cell adhesion and migration</subject><subject>Cell Shape</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>chemokines</subject><subject>Coculture Techniques</subject><subject>Guanine Nucleotide Exchange Factors - metabolism</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Integrin alpha4beta1 - metabolism</subject><subject>Integrin alpha5beta1 - metabolism</subject><subject>integrins</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>K562 Cells</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lysophospholipids - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>multiple myeloma</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - immunology</subject><subject>Multiple Myeloma - metabolism</subject><subject>Multiple Myeloma - pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>rac1 GTP-Binding Protein - metabolism</subject><subject>Receptors, Lysosphingolipid - genetics</subject><subject>Receptors, Lysosphingolipid - metabolism</subject><subject>RNA Interference</subject><subject>Signal Transduction</subject><subject>signalling</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - metabolism</subject><subject>Stromal Cells - immunology</subject><subject>Stromal Cells - metabolism</subject><subject>Stromal Cells - pathology</subject><subject>Talin - metabolism</subject><subject>Time Factors</subject><subject>Transendothelial and Transepithelial Migration</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1O3DAUhS0EKlPoghdA2bDoImDHPxkvEYIZJEqRoOrSuuPYE5ckjuzMtKM-VXkQnqmOZqCrru7P-e650kHohOBzgnFx0cNQnzMsxB6aECxFLqdS7KNJ0oqcMlIeoo8x_sAYS8n5B3RYFCUhXLAJ-v3Y165b-ug6k5O8r33saxhMBnpw69TETNem9c-j3gff-sFUWbsxjW8h06ZpMqhqE53vMuiS4pYBhnFy3do36-Sdvf5hry8kLQazDK7L7KrTI3KMDiw00Xza1SP07eb66Wqe332d3V5d3uWaCSLyglcMM0Ysw5URGBjFRDOwWIuiZHgqNTdCpt5avLC0oKVcFBIqXlIKC07pEfq89dXBxxiMVX1wLYSNIliNAaoxQDUGmNjTLduvFq2p3sm3xBJwtgMgamhsgE67-I8TJRclJYm72HI_XWM2__-oHi6f5rvX-fbCxcH8er-A8KySY8nV9_uZms4oZ1_4XD3Sv4fCmhI</recordid><startdate>201301</startdate><enddate>201301</enddate><creator>García-Bernal, David</creator><creator>Redondo-Muñoz, Javier</creator><creator>Dios-Esponera, Ana</creator><creator>Chèvre, Raphaël</creator><creator>Bailón, Elvira</creator><creator>Garayoa, Mercedes</creator><creator>Arellano-Sánchez, Nohemí</creator><creator>Gutierrez, Norma C</creator><creator>Hidalgo, Andrés</creator><creator>García-Pardo, Angeles</creator><creator>Teixidó, Joaquin</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</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></search><sort><creationdate>201301</creationdate><title>Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function</title><author>García-Bernal, David ; Redondo-Muñoz, Javier ; Dios-Esponera, Ana ; Chèvre, Raphaël ; Bailón, Elvira ; Garayoa, Mercedes ; Arellano-Sánchez, Nohemí ; Gutierrez, Norma C ; Hidalgo, Andrés ; García-Pardo, Angeles ; Teixidó, Joaquin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4616-25d40441f40de60a4301c4af0c6274089c5e69627ff0bf32379b29ad5733ab533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>bone marrow</topic><topic>Bone Marrow - blood supply</topic><topic>Bone Marrow - immunology</topic><topic>Bone Marrow - metabolism</topic><topic>Bone Marrow - pathology</topic><topic>Cell Adhesion</topic><topic>cell adhesion and migration</topic><topic>Cell Shape</topic><topic>Chemokine CXCL12 - metabolism</topic><topic>chemokines</topic><topic>Coculture Techniques</topic><topic>Guanine Nucleotide Exchange Factors - metabolism</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Integrin alpha4beta1 - metabolism</topic><topic>Integrin alpha5beta1 - metabolism</topic><topic>integrins</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>K562 Cells</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lysophospholipids - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>multiple myeloma</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - immunology</topic><topic>Multiple Myeloma - metabolism</topic><topic>Multiple Myeloma - pathology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>rac1 GTP-Binding Protein - metabolism</topic><topic>Receptors, Lysosphingolipid - genetics</topic><topic>Receptors, Lysosphingolipid - metabolism</topic><topic>RNA Interference</topic><topic>Signal Transduction</topic><topic>signalling</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine - metabolism</topic><topic>Stromal Cells - immunology</topic><topic>Stromal Cells - metabolism</topic><topic>Stromal Cells - pathology</topic><topic>Talin - metabolism</topic><topic>Time Factors</topic><topic>Transendothelial and Transepithelial Migration</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>García-Bernal, David</creatorcontrib><creatorcontrib>Redondo-Muñoz, Javier</creatorcontrib><creatorcontrib>Dios-Esponera, Ana</creatorcontrib><creatorcontrib>Chèvre, Raphaël</creatorcontrib><creatorcontrib>Bailón, Elvira</creatorcontrib><creatorcontrib>Garayoa, Mercedes</creatorcontrib><creatorcontrib>Arellano-Sánchez, Nohemí</creatorcontrib><creatorcontrib>Gutierrez, Norma C</creatorcontrib><creatorcontrib>Hidalgo, Andrés</creatorcontrib><creatorcontrib>García-Pardo, Angeles</creatorcontrib><creatorcontrib>Teixidó, Joaquin</creatorcontrib><collection>Istex</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><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>García-Bernal, David</au><au>Redondo-Muñoz, Javier</au><au>Dios-Esponera, Ana</au><au>Chèvre, Raphaël</au><au>Bailón, Elvira</au><au>Garayoa, Mercedes</au><au>Arellano-Sánchez, Nohemí</au><au>Gutierrez, Norma C</au><au>Hidalgo, Andrés</au><au>García-Pardo, Angeles</au><au>Teixidó, Joaquin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>2013-01</date><risdate>2013</risdate><volume>229</volume><issue>1</issue><spage>36</spage><epage>48</epage><pages>36-48</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><coden>JPTLAS</coden><abstract>Myeloma cell adhesion dependent on α4β1 integrin is crucial for the progression of multiple myeloma (MM). The α4β1‐dependent myeloma cell adhesion is up‐regulated by the chemokine CXCL12, and pharmacological blockade of the CXCL12 receptor CXCR4 leads to defective myeloma cell homing to bone marrow (BM). Sphingosine‐1‐phosphate (S1P) regulates immune cell trafficking upon binding to G‐protein‐coupled receptors. Here we show that myeloma cells express S1P1, a receptor for S1P. We found that S1P up‐regulated the α4β1‐mediated myeloma cell adhesion and transendothelial migration stimulated by CXCL12. S1P promoted generation of high‐affinity α4β1 that efficiently bound the α4β1 ligand VCAM‐1, a finding that was associated with S1P‐triggered increase in talin‐β1 integrin association. Furthermore, S1P cooperated with CXCL12 for enhancement of α4β1‐dependent adhesion strengthening and spreading. CXCL12 and S1P activated the DOCK2‐Rac1 pathway, which was required for stimulation of myeloma cell adhesion involving α4β1. Moreover, in vivo analyses indicated that S1P contributes to optimizing the interactions of MM cells with the BM microvasculture and for their lodging inside the bone marrow. The regulation of α4β1‐dependent adhesion and migration of myeloma cells by CXCL12‐S1P combined activities might have important consequences for myeloma disease progression. Copyright © 2012 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>22711564</pmid><doi>10.1002/path.4066</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of pathology, 2013-01, Vol.229 (1), p.36-48 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Biological and medical sciences bone marrow Bone Marrow - blood supply Bone Marrow - immunology Bone Marrow - metabolism Bone Marrow - pathology Cell Adhesion cell adhesion and migration Cell Shape Chemokine CXCL12 - metabolism chemokines Coculture Techniques Guanine Nucleotide Exchange Factors - metabolism Hematologic and hematopoietic diseases Humans Immunodeficiencies. Immunoglobulinopathies Immunoglobulinopathies Immunopathology Integrin alpha4beta1 - metabolism Integrin alpha5beta1 - metabolism integrins Investigative techniques, diagnostic techniques (general aspects) K562 Cells Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lysophospholipids - metabolism Medical sciences Mice Mice, Inbred NOD Mice, SCID multiple myeloma Multiple Myeloma - genetics Multiple Myeloma - immunology Multiple Myeloma - metabolism Multiple Myeloma - pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques rac1 GTP-Binding Protein - metabolism Receptors, Lysosphingolipid - genetics Receptors, Lysosphingolipid - metabolism RNA Interference Signal Transduction signalling Sphingosine - analogs & derivatives Sphingosine - metabolism Stromal Cells - immunology Stromal Cells - metabolism Stromal Cells - pathology Talin - metabolism Time Factors Transendothelial and Transepithelial Migration Transfection Tumor Cells, Cultured Vascular Cell Adhesion Molecule-1 - metabolism |
| title | Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function |
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