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

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

Author Perez, Elizabeth Cristina Autor UNIFESP Google Scholar
Machado, Joel Autor UNIFESP Google Scholar
Aliperti, Fabiana Autor UNIFESP Google Scholar
Freymueller, Edna Autor UNIFESP Google Scholar
Mariano, Mario Autor UNIFESP Google Scholar
Lopes, Jose Daniel Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Language English
Date 2008-05-01
Published in Cancer Science. Oxford: Blackwell Publishing, v. 99, n. 5, p. 920-928, 2008.
ISSN 1347-9032 (Sherpa/Romeo, impact factor)
Publisher Blackwell Publishing
Extent 920-928
Origin http://dx.doi.org/10.1111/j.1349-7006.2008.00776.x
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000254609300014
URI http://repositorio.unifesp.br/handle/11600/30614

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