The axis IL-10/claudin-10 is implicated in the modulation of aggressiveness of melanoma cells by B-1 lymphocytes

The axis IL-10/claudin-10 is implicated in the modulation of aggressiveness of melanoma cells by B-1 lymphocytes

Author Perez, Elizabeth Cristina Google Scholar
Xander, Patricia Autor UNIFESP Google Scholar
Lucatelli Laurindo, Maria Fernanda Autor UNIFESP Google Scholar
Novaes e Brito, Ronni Romulo Google Scholar
Vivanco, Bruno Camolese Autor UNIFESP Google Scholar
Mortara, Renato Arruda Autor UNIFESP Google Scholar
Mariano, Mario Autor UNIFESP Google Scholar
Lopes, Jose Daniel Autor UNIFESP Google Scholar
Keller, Alexandre Castro Autor UNIFESP Google Scholar
Abstract B-1 lymphocytes are known to increase the metastatic potential of B16F10 melanoma cells via the extracellular signal-regulated kinase (ERK) pathway. Since IL-10 is associated with B-1 cells performance, we hypothesized that IL-10 could be implicated in the progression of melanoma. In the present work, we found that the C57BL/6 mice, inoculated with B16F10 cells that were co-cultivated with B-1 lymphocytes from IL-10 knockout mice, developed fewer metastatic nodules than the ones which were injected with the melanoma cells that were cultivated in the presence of wild-type B-1 cells. The impairment of metastatic potential of the B16F10 cells was correlated with low activation of the ERK signaling pathway, supporting the idea that the production of IL-10 by B-1 cells influences the behavior of the tumor. A microarray analysis of the B-1 lymphocytes revealed that IL-10 deficiency is associated with down-regulation of the genes that code for claudin-10, a protein that is involved in cell-to-cell contact and that has been linked to lung adenocarcinoma. In order to determine the impact of claudin-10 in the cross-talk between B-1 lymphocytes and the B16F10 tumor cells, we took advantage of small interfering RNA. The silencing of claudin-10 gene in B-1 lymphocytes inhibited activation of the ERK pathway and abrogated the B-1-induced aggressive behavior of the B16F10 cells. Thus, our findings suggest that the axis IL-10/claudin-10 is a promising target for the development of therapeutic agents against aggressive melanoma.
xmlui.dri2xhtml.METS-1.0.item-coverage San Francisco
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Grant number FAPESP: 11/50256-6
FAPESP: 08/50632-5
FAPESP: 2016/02189-1
CNPq: 472035/2011-8
CNPq: 308374/2016-9
Date 2017
Published in Plos One. San Francisco, v. 12, n. 11, p. -, 2017.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent -
Origin http://dx.doi.org/10.1371/journal.pone.0187333
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000415378800015
URI https://repositorio.unifesp.br/handle/11600/58166

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