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

• DOI: 10.1371/journal.pone.0187333
• Publication Date: 2017-11-16T21:01:48Z
• Authors: Elizabeth Cristin...; Patricia Xander; Maria Fernanda Lu...; Ronni Rômulo Nova...; Bruno Camolese Vi...; Renato Arruda Mor...; Mario Mariano; José Daniel Lopes; Alexandre Castro ...
• Keywords: 570; 0303 health sciences; Science; Q; R; Melanoma, Experimental; Interleukin-10; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cell Line, Tumor; Claudins; Medicine; Animals; Neoplasm Metastasis; Research Article

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.