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

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.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Univ Paulista, Environm & Expt Pathol Program, Sao Paulo, SP, BrazilUniv Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmaceut Sci, Campus Diadema, Diadema, SP, BrazilCtr Univ Sao Camilo, Sao Paulo, SP, BrazilUniv Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Nephrol Div, Dept Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmaceut Sci, Campus Diadema, Diadema, SP, BrazilUniv Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Nephrol Div, Dept Med, Sao Paulo, SP, BrazilFAPESP: 11/50256-6FAPESP: 08/50632-5FAPESP: 2016/02189-1CNPq: 472035/2011-8CNPq: 308374/2016-9Web of Scienc