Crosstalk between B16 melanoma cells and B-1 lymphocytes induces global changes in tumor cell gene expression

Crosstalk between B16 melanoma cells and B-1 lymphocytes induces global changes in tumor cell gene expression

Author Xander, Patricia Autor UNIFESP Google Scholar
Novaes e Brito, Ronni Romulo Google Scholar
Perez, Elizabeth Cristina Google Scholar
Pozzibon, Jaqueline Maciel Autor UNIFESP Google Scholar
Souza, Camila Ferreira de Autor UNIFESP Google Scholar
Pellegrino, Renata Autor UNIFESP Google Scholar
Bernardo, Viviane Autor UNIFESP Google Scholar
Jasiulionis, Miriam Galvonas Autor UNIFESP Google Scholar
Mariano, Mario Autor UNIFESP Google Scholar
Lopes, Jose Daniel Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Ctr Univ Sao Camilo
Abstract The analysis of gene expression patterns in cancers has improved the understanding of the mechanisms underlying the process of metastatic progression. However, the acquisition of invasive behavior in melanoma is poorly understood. in melanoma, components of the immune system can contribute to tumor progression, and inflammatory cells can influence almost all aspects of cancer progression, including metastasis. Recent studies have attributed an important role to B-1 cells, a subset of B lymphocytes, in melanoma progression. in vitro interactions between B16 melanoma cells and B-1 lymphocytes lead to increased B16 cell metastatic potential, but the molecular changes induced by B-1 lymphocytes on B16 cells have not yet been elucidated. in this study, we used a microarray approach to assess the gene expression profile of B16 melanoma cells following contact with B-1 lymphocytes (B16B1). the microarray analysis identified upregulation in genes involved with metastatic progression, such as ctss, ccl5, cxcl2 and stat3. RT-qPCR confirmed this increase in mRNA expression in B16B1 samples. As previous studies have indicated that the ERK1/2 MAPK cascade is activated in melanoma cells following contact with B-1 lymphocytes, RT-qPCR was performed with RNA from melanoma cells before and after contacting B-1 cells and untreated or treated with ERK phosphorylation inhibitors. the results showed that the expression of stat3, ctss and cxcl2 increased in B16B1 but decreased following ERK1/2 MAPK inhibition. Ccl5 gene expression increased after contacting B-1 cells and was maintained at the same level following inhibitor treatment. Stat3 was verified and validated at the protein level by Western blot analysis. STAT3 expression was also significantly increased in B16B1, suggesting that this pathway can also contribute to the increased metastatic phenotype observed in our model. These results indicated that B-1 cells induce important global gene expression changes in B16 melanoma cells. We also evaluated the relationship of some of the genes identified as differentially expressed and the ERK1/2 MAPK cascade. This work may have important implications for understanding the role of B-1 lymphocytes and the ERK/MAPK cascade in the metastatic process. (C) 2013 Elsevier GmbH. All rights reserved.
Keywords B-1 cells
Melanoma
Microarray
Gene expression
Metastases
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2007/51501-9
FAPESP: 2007/50521-6
CNPq: 502452/2008-0
Date 2013-10-01
Published in Immunobiology. Jena: Elsevier Gmbh, Urban & Fischer Verlag, v. 218, n. 10, p. 1293-1303, 2013.
ISSN 0171-2985 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1293-1303
Origin http://dx.doi.org/10.1016/j.imbio.2013.04.017
Access rights Closed access
Type Article
Web of Science ID WOS:000323588900009
URI http://repositorio.unifesp.br/handle/11600/36820

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