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dc.contributor.author
Borge, Mercedes
dc.contributor.author
Remes Lenicov, Federico
dc.contributor.author
Nannini, Paula Romina
dc.contributor.author
Alicandú, María M. de los Ríos
dc.contributor.author
Podaza, Enrique Arturo
dc.contributor.author
Ceballos, Ana
dc.contributor.author
Fernandez Grecco, Horacio
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Cabrejo, María
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Bezares, Raimundo F.
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Morande, Pablo Elías
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Oppezzo, Pablo
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Giordano, Mirta Nilda
dc.contributor.author
Gamberale, Romina
dc.date.available
2017-12-28T14:08:41Z
dc.date.issued
2014-09
dc.identifier.citation
Gamberale, Romina; Giordano, Mirta Nilda; Oppezzo, Pablo; Morande, Pablo Elías; Bezares, Raimundo F.; Cabrejo, María; et al.; The Expression of Sphingosine-1 Phosphate Receptor-1 in Chronic Lymphocytic Leukemia Cells Is Impaired by Tumor Microenvironmental Signals and Enhanced by Piceatannol and R406; American Association of Immunologists; Journal of Immunology; 193; 6; 9-2014; 3165-3174
dc.identifier.issn
0022-1767
dc.identifier.uri
http://hdl.handle.net/11336/31770
dc.description.abstract
Chronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of clonal B lymphocytes. Proliferation occurs in lymphoid tissues upon interaction of leukemic cells with a supportive microenvironment. Therefore, the mobilization of tissue-resident CLL cells into the circulation is a useful therapeutic strategy to minimize the reservoir of tumor cells within survival niches. Because the exit of normal lymphocytes from lymphoid tissues depends on the presence of sphingosine-1 phosphate (S1P) and the regulated expression of S1P receptor-1 (S1PR1), we investigated whether the expression and function of S1PR1 can be modulated by key microenvironment signals. We found that activation of CLLcells with CXCL12, fibroblast CD40L(+), BCR cross-linking, or autologous nurse-like cells reduces their S1PR1 expression and the migratory response toward S1P. Moreover, we found that S1PR1 expression was reduced in the proliferative/activated subset of leukemic cells compared with the quiescent subset from the same patient. Similarly, bone marrow-resident CLL cells expressing high levels of the activation marker CD38 showed a lower expression of S1PR1 compared with CD38(low) counterparts. Finally, given that treatment with BCR-associated kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1 might modulate the egress of the leukemic clone from lymphoid tissues.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Association of Immunologists
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Llc
dc.subject
Sphingosine-1-Phosphate
dc.subject.classification
Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
The Expression of Sphingosine-1 Phosphate Receptor-1 in Chronic Lymphocytic Leukemia Cells Is Impaired by Tumor Microenvironmental Signals and Enhanced by Piceatannol and R406
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-12-15T14:54:39Z
dc.journal.volume
193
dc.journal.number
6
dc.journal.pagination
3165-3174
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Borge, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Remes Lenicov, Federico. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
dc.description.fil
Fil: Nannini, Paula Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Alicandú, María M. de los Ríos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Podaza, Enrique Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Ceballos, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
dc.description.fil
Fil: Fernandez Grecco, Horacio. Sanatorio Municipal Dr. Julio Méndez; Argentina
dc.description.fil
Fil: Cabrejo, María. Sanatorio Municipal Dr. Julio Méndez; Argentina
dc.description.fil
Fil: Bezares, Raimundo F.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; Argentina
dc.description.fil
Fil: Morande, Pablo Elías. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Oppezzo, Pablo. Instituto Pasteur de Montevideo; Uruguay
dc.description.fil
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.journal.title
Journal of Immunology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/193/6/3165.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.4049/jimmunol.1400547


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