Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function

51 p.-7 fig.-1 tab.-2 fig.supl.

Detalles Bibliográficos
Autores: García-Bernal, David, Redondo-Muñoz, Javier, Dios-Esponera, Ana, Chèvre, Raphael, Bailón, Elvira, Garayoa, Mercedes, Arellano-Sánchez, Nohemí, Gutiérrez, Norma C., Hidalgo, Andrés, García-Pardo, Angeles, Teixidó, Joaquín
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/66990
Acceso en línea:http://hdl.handle.net/10261/66990
Access Level:acceso abierto
Palabra clave:Multiple myeloma
Chemokines
Cell adhesion and migration
Integrins
Bone marrow
Signalling
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spelling Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin functionGarcía-Bernal, DavidRedondo-Muñoz, JavierDios-Esponera, AnaChèvre, RaphaelBailón, ElviraGarayoa, MercedesArellano-Sánchez, NohemíGutiérrez, Norma C.Hidalgo, AndrésGarcía-Pardo, AngelesTeixidó, JoaquínMultiple myelomaChemokinesCell adhesion and migrationIntegrinsBone marrowSignalling51 p.-7 fig.-1 tab.-2 fig.supl.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 progressionThis study was supported by the Ministerio de Ciencia e Innovación (Grant Nos SAF2011-24022 to JT, SAF2009-07035 to AGP, SAF2009-11037 to AH, RD06/0020/0011 to JT and AGP, RD06/0020/0006 to NCG and MG and PI081825 to MG), the Comunidad de Madrid (Grant No. P2010/BMD-2314 to AGP, JT and AH) and the Fundación de Investigación Médica Mutua Madrileña (to AGP and MG). AH was also funded by the FP7-People-2009-RG (Grant No. 246655), a Ramón y Cajal Fellowship (Grant No. RYC-2007-00697) and the Pro-CNIC Foundation.Peer reviewedJohn Wiley & Sons201320132013info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/66990reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp:dx.doi.org/10.1002/path.4066info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/669902026-05-22T06:33:51Z
dc.title.none.fl_str_mv Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
title Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
spellingShingle Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
García-Bernal, David
Multiple myeloma
Chemokines
Cell adhesion and migration
Integrins
Bone marrow
Signalling
title_short Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
title_full Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
title_fullStr Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
title_full_unstemmed Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
title_sort Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function
dc.creator.none.fl_str_mv García-Bernal, David
Redondo-Muñoz, Javier
Dios-Esponera, Ana
Chèvre, Raphael
Bailón, Elvira
Garayoa, Mercedes
Arellano-Sánchez, Nohemí
Gutiérrez, Norma C.
Hidalgo, Andrés
García-Pardo, Angeles
Teixidó, Joaquín
author García-Bernal, David
author_facet García-Bernal, David
Redondo-Muñoz, Javier
Dios-Esponera, Ana
Chèvre, Raphael
Bailón, Elvira
Garayoa, Mercedes
Arellano-Sánchez, Nohemí
Gutiérrez, Norma C.
Hidalgo, Andrés
García-Pardo, Angeles
Teixidó, Joaquín
author_role author
author2 Redondo-Muñoz, Javier
Dios-Esponera, Ana
Chèvre, Raphael
Bailón, Elvira
Garayoa, Mercedes
Arellano-Sánchez, Nohemí
Gutiérrez, Norma C.
Hidalgo, Andrés
García-Pardo, Angeles
Teixidó, Joaquín
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Multiple myeloma
Chemokines
Cell adhesion and migration
Integrins
Bone marrow
Signalling
topic Multiple myeloma
Chemokines
Cell adhesion and migration
Integrins
Bone marrow
Signalling
description 51 p.-7 fig.-1 tab.-2 fig.supl.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013
2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/66990
url http://hdl.handle.net/10261/66990
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http:dx.doi.org/10.1002/path.4066
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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