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

Author(s)

Perez, Elizabeth Cristina ^{[1, 2]} ; Xander, Patricia ^[3] ; Lucatelli Laurindo, Maria Fernanda ^[1] ; Novaes e Brito, Ronni Romulo ^[4] ; Vivanco, Bruno Camolese ^[1] ; Mortara, Renato Arruda ^[1] ; Mariano, Mario ^{[1, 2]} ; Lopes, Jose Daniel ^[1] ; Keller, Alexandre Castro ^{[1, 5]}

Affiliation

^[1] Univ Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP - Brazil

^[2] Univ Paulista, Environm & Expt Pathol Program, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Campus Diadema, Diadema, SP - Brazil

^[4] Ctr Univ Sao Camilo, Sao Paulo, SP - Brazil

^[5] Univ Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Nephrol Div, Dept Med, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 12, n. 11 NOV 16 2017.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 11/50256-6 - B-1 cells: biology, relations with other cells of the immune system and participation in different experimental models
• Grantee: José Daniel Lopes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/02189-1 - Incorporation of glycosphingolipids into nanoparticles to immunotherapy using invariant Natural Killer T lymphocytes
• Grantee: Alexandre de Castro Keller
• Support Opportunities: Regular Research Grants