B-1 lymphocytes increase metastatic behavior of melanoma cells through the extracellular signal-regulated kinase pathway

Autor(es)

Pérez, Elizabeth Cristina ; Machado Júnior, Joel ; Aliperti, Fabiana ; Freymuller, Edna ; Mariano, Mario ; Lopes, José Daniel ^[6]

• Tipo de documento: Artigo Científico
• Fonte: Cancer Science; v. 99, n. 5, p. 920-928, May 2008.
• Área do conhecimento: Ciências Biológicas - Imunologia
• Assunto(s): Melanoma Células sanguíneas Linfócitos B

Resumo

Increasing evidence indicates that tumors require a constant influx of myelomonocytic cells to support their malignant behavior. This is caused by tumor-derived factors, which recruit and induce functional differentiation of myelomonocytic cells, most of which are macrophages. Although myeloid lineages are the classical precursors of macrophages, B-lymphoid lineages such as B-1 cells, a subset of B-lymphocytes found predominantly in pleural and peritoneal cavities, are also able to migrate to inflammatory sites and differentiate into mononuclear phagocytes exhibiting macrophage-like phenotypes. Here we examined the interplay of B-1 cells and tumor cells, and checked whether this interaction provides signals to influence melanoma cells metastases. Using in vitro coculture experiments we showed that B16, a murine melanoma cell line, and B-1 cells physically interact. Moreover, interaction of B16 with B-1 cells leads to up-regulation of metastasis-related gene expression (MMP-9 and CXCR-4), increasing its metastatic potential, as revealed by experimental metastases assays in vivo. We also provide evidence that B16 cells exhibit markedly up-regulated phosphorylation of the extracellular signal-regulated kinase (ERK) when cocultured with B-1 cells. Inhibition of ERK phosphorylation induced by B-1 cells with inhibitors of MEK1/2 strongly suppressed the induction of MMP-9 and CXCR-4 mRNA expression and impaired the increased metastatic behavior of B16. In addition, constitutive levels of ERK1/2 phosphorylation in B-1 cells are necessary for their commitment to affect the metastatic potential of B16 cells. Our findings show for the first time that B-1 lymphocytes can contribute to tumor cell properties required for invasiveness during metastatic spread. (AU)

• Processo FAPESP: 02/06935-7 - Controle epigenético da progressão tumoral de melanócitos
• Beneficiário: Joel Machado Junior
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 03/05176-8 - Estudo da modificacao fenotipica do melanoma induzida pela interacao com celulas b-1 em modelo murino - mecanismos de transducao de sinal.
• Beneficiário: ELIZABETH CRISTINA PEREZ HURTADO
• Modalidade de apoio: Bolsas no Brasil - Doutorado