English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/131855
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

In vivo adhesion of malignant B cells to bone marrow microvasculature is regulated by α4β1 cytoplasmic-binding proteins

AutorMartínez-Moreno, Mónica; Aguilera-Montilla, Noemí ; Sevilla-Movilla, Silvia; Isern de Val, Soledad; Arellano-Sánchez, Nohemí ; García-Pardo, Angeles ; Teixidó, Joaquín
Palabras claveMultiple Myeloma
Chronic lymphocytic leukemia
Cell trafficking
Integrins
Intravital Microscopy
Fecha de publicación10-dic-2015
EditorNature Publishing Group
CitaciónLeukemia (2015)
ResumenMultiple myeloma (MM) and chronic lymphocytic leukemia (CLL) cells must attach to the bone marrow (BM) microvasculature before lodging in the BM microenvironment. Using intravital microscopy (IVM) of the BM calvariae we demonstrate that the α4β1 integrin is required for MM and CLL cell firm arrest onto the BM microvasculature, while endothelial P-selectin and E-selectin mediate cell rolling. Talin, kindlin-3 and ICAP-1 are β1-integrin-binding partners that regulate β1-mediated cell adhesion. We show that talin and kindlin-3 cooperatively stimulate high affinity and strength of α4β1-dependent MM and CLL cell attachment, whereas ICAP-1 negatively regulates this adhesion. A functional connection between talin/kindlin-3 and Rac1 was found to be required for MM cell attachment mediated by α4β1. Importantly, IVM analyses with talin- and kindlin-3-silenced MM cells indicate that these proteins are needed for cell arrest on the BM microvasculature. Instead, MM cell arrest is repressed by ICAP-1. Moreover, MM cells silenced for talin and kindlin-3, and cultured on α4β1 ligands showed higher susceptibility to bortezomib-mediated cell apoptosis. Our results highlight the requirement of α4β1 and selectins for the in vivo attachment of MM and CLL cells to the BM microvasculature, and indicate that talin, kindlin-3 and ICAP-1 differentially control physiological adhesion by regulating α4β1 activity.
Descripción40 p.-7 fig. Martínez-Moreno, Mónica et al.
Versión del editorhttp://dx.doi.org/ 10.1038/leu.2015.332
URIhttp://hdl.handle.net/10261/131855
DOI10.1038/leu.2015.332
ISSN0887-6924
E-ISSN1476-5551
Aparece en las colecciones: (CIB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Leukemia_2015.pdfPostprint1,02 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.