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

MARÍA J. RICO*1,2, PABLO MATAR*1,2, O. GRACIELA SCHAROVSKY1,3
1. Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, (2000) Rosario, Argentina.
2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).
3. Consejo de Investigaciones, UNR; Rosario, Argentina.
* Address correspondence to: O. G. Scharovsky. E-mail:

BIOCELL 2012, 36(2), 91-95. https://doi.org/10.32604/biocell.2012.36.091

Abstract

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 IL10 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 vivo 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.

Keywords

metastasis, cyclophosphamide, cell proliferation

Cite This Article

RICO, M. J., MATAR, P., SCHAROVSKY, O. G. (2012). Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma. BIOCELL, 36(2), 91–95.



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