Modificação fenotípica do melanoma murino induzida pela interação com células B-1 - Mecanismos de transdução de sinal. / B-1 lymphocytes increase metastatic behavior of melanoma cells through the extracellular signal-regulated kinase pathway.

AUTOR(ES)

Elizabeth Cristina Pérez Hurtado

DATA DE PUBLICAÇÃO

2007

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 phenotype. 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 upregulation of metastasis-related genes expression (MMP-9 and CXCR-4), increasing its metastatic potential, as revealed by experimental metastases assays in vivo. We also provide evidences that B16 cells exhibit markedly upregulated phosphorylation of the extracellular signalregulated kinase (ERK) when co-cultured with B-1 cells. Inhibition of ERK phosphorylation induced by B-1 cells with an inhibitor 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 80 lymphocytes can contribute to tumor cell properties required for invasiveness during metastatic spread.

ASSUNTO(S)

1. células b16. 2. linfócitos b-1. 3. erk. 4. metástases. parasitologia

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