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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Microambiente tumoral > DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista >

Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation
Authors: Alfaro, C. (Carlos)
Suarez, N. (Natalia)
Martinez-Forero, I. (Iván)
Palazon, A. (Asís)
Rouzaut, A. (Ana)
Solano, S. (Sarai)
Feijoo, E. (Esperanza)
Gurpide, A. (Alfonso)
Bolaños, E. (Elixabet)
Erro, L. (Lorena)
Dubrot, J. (Juan)
Hervas-Stubbs, S. (Sandra)
Gonzalez, A. (Alvaro)
Perez-Gracia, J.L. (José Luis)
Melero, I. (Ignacio)
Keywords: Cell Movement/drug effects
Dendritic Cells/drug effects
Dendritic Cells/pathology
Interleukin-8/pharmacology
Lymphocyte Activation/drug effects
Neoplasms/metabolism
T-Lymphocytes/immunology
Issue Date: 2011
Publisher: Public Library of Science
Publisher version: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017922
ISSN: 1932-6203
Citation: Alfaro C, Suarez N, Martinez-Forero I, Palazon A, Rouzaut A, Solano S, et al. Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation. PLoS One 2011 Mar 14;6(3):e17922
Abstract
BACKGROUND: Interleukin-8 (IL-8, CXCL8) is readily produced by human malignant cells. Dendritic cells (DC) both produce IL-8 and express the IL-8 functional receptors CXCR1 and CXCR2. Most human colon carcinomas produce IL-8. IL-8 importance in malignancies has been ascribed to angiogenesis promotion. PRINCIPAL FINDINGS: IL-8 effects on human monocyte-derived DC biology were explored upon DC exposure to recombinant IL-8 and with the help of an IL-8 neutralizing mAb. In vivo experiments were performed in immunodeficient mice xenografted with IL-8-producing human colon carcinomas and comparatively with cell lines that do not produce IL-8. Allogenic T lymphocyte stimulation by DC was explored under the influence of IL-8. DC and neutrophil chemotaxis were measured by transwell-migration assays. Sera from tumor-xenografted mice contained increasing concentrations of IL-8 as the tumors progress. IL-8 production by carcinoma cells can be modulated by low doses of cyclophosphamide at the transcription level. If human DC are injected into HT29 or CaCo2 xenografted tumors, DC are retained intratumorally in an IL-8-dependent fashion. However, IL-8 did not modify the ability of DC to stimulate T cells. Interestingly, pre-exposure of DC to IL-8 desensitizes such cells for IL-8-mediated in vitro or in vivo chemoattraction. Thereby DC become disoriented to subsequently follow IL-8 chemotactic gradients towards malignant or inflamed tissue. CONCLUSIONS: IL-8 as produced by carcinoma cells changes DC migration cues, without directly interfering with DC-mediated T-cell stimulation.
Permanent link: http://hdl.handle.net/10171/20286
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista
DA - CUN - Oncología médica - Artículos de revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - Ciencias - Bioquímica y Biología molecular - Artículos de Revista
DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista

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