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dc.contributor.authorGarcía-Bernal, David-
dc.contributor.authorRedondo-Muñoz, Javier-
dc.contributor.authorDios-Esponera, Ana-
dc.contributor.authorChèvre, Raphaël-
dc.contributor.authorBailón, Elvira-
dc.contributor.authorGarayoa, Mercedes-
dc.contributor.authorArellano-Sánchez, Nohemí-
dc.contributor.authorGutiérrez, Norma C.-
dc.contributor.authorHidalgo, Andrés-
dc.contributor.authorGarcía-Pardo, Angeles-
dc.contributor.authorTeixidó, Joaquín-
dc.identifier.citationThe Journal of Pathology, 229 (1) : 36-48 (2013)es_ES
dc.description51 p.-7 fig.-1 tab.-2 fig.supl.es_ES
dc.description.abstractMyeloma 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 progressiones_ES
dc.description.sponsorshipThis 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.es_ES
dc.publisherJohn Wiley & Sonses_ES
dc.subjectMultiple myelomaes_ES
dc.subjectCell adhesion and migrationes_ES
dc.subjectBone marrowes_ES
dc.titleSphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin functiones_ES
dc.description.peerreviewedPeer reviewedes_ES
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