Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma

We have already shown that IL-10 plays an important role in immunosuppression and metastatic dissemination in the rat B-cell lymphoma L-TACB model. It was suggested that the up-regulation of IL-10 production and IL-10 receptor (IL-10R) expression would be part of the transition from primary tumor to...

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Autores principales: Rico, María José, Matar, Pablo, Scharovsky, O. Graciela
Formato: artículo publishedVersion article
Lenguaje:Inglés
Publicado: Sociedad Latinoamericana de Microscopía Electrónica. Centro Regional de Investigaciones Científicas y Tecnológicas (Mendoza, Argentina) 2013
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Acceso en línea:http://hdl.handle.net/2133/2547
http://hdl.handle.net/2133/2547
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id I15-R121-2133-2547
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv en
topic Metastasis
Cyclophosphamide
Cell proliferation
spellingShingle Metastasis
Cyclophosphamide
Cell proliferation
Rico, María José
Matar, Pablo
Scharovsky, O. Graciela
Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma
topic_facet Metastasis
Cyclophosphamide
Cell proliferation
description We have already shown that IL-10 plays an important role in immunosuppression and metastatic dissemination in the rat B-cell lymphoma L-TACB model. It was suggested that the up-regulation of IL-10 production and IL-10 receptor (IL-10R) expression would be part of the transition from primary tumor to metastatic phenotype and that IL-10, besides its immunosuppressive activity, may act as a growth factor for metastatic L-TACB cells. The treatment of L-TACB-bearing rats with a single low-dose cyclophosphamide decreased IL-10 production, reverted immunosuppression and induced the immunologic rejection of tumor metastasis without any effect on primary tumor growth. Our current aim was to investigate the effects of cyclophosphamide on the expression of IL-10 and IL-10R on primary and metastatic L-TACB cells. Considering that cyclophosphamide is a prodrug, we used mafosfamide, a compound that yields in vitro the same active metabolites as cyclophosphamide does in vivo. Mafosfamide induced down-regulation of IL-10 production and IL-10R expression on metastatic cells and, concomitantly, inhibited metastatic cell proliferation. We suggest that mafosfamide would inhibit the regulatory loop mediated by the IL-10/IL-10R system and, as a consequence, metastatic cell proliferation. These results may have a considerable impact on the design of new therapies for metastatic lymphomas.
format artículo
publishedVersion
article
author Rico, María José
Matar, Pablo
Scharovsky, O. Graciela
author_facet Rico, María José
Matar, Pablo
Scharovsky, O. Graciela
author_sort Rico, María José
title Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma
title_short Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma
title_full Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma
title_fullStr Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma
title_full_unstemmed Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma
title_sort modulation of il-10/il-10r expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat b-cell lymphoma
publisher Sociedad Latinoamericana de Microscopía Electrónica. Centro Regional de Investigaciones Científicas y Tecnológicas (Mendoza, Argentina)
publishDate 2013
url http://hdl.handle.net/2133/2547
http://hdl.handle.net/2133/2547
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AT matarpablo modulationofil10il10rexpressionbymafosfamideaderivativeof4hydroxycyclophosphamideinaratbcelllymphoma
AT scharovskyograciela modulationofil10il10rexpressionbymafosfamideaderivativeof4hydroxycyclophosphamideinaratbcelllymphoma
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