BDE-209 and TCDD enhance metastatic characteristics of melanoma cells after chronic exposure

• Published in: Environmental pollution (1987) 2022-11, Vol.313, p.120140-120140, Article 120140
• Main Authors: Silva Filho, Benisio Ferreira, Filipak Neto, Francisco, Marchi, Micheli de, Moggio, Erick Laurent, Rossi, Izadora Volpato, Sabatke, Bruna, Ramirez, Marcel Ivan, Lucena, Miguel Clodomiro dos Santos, Todeschini, Adriane Regina, Oliveira Ribeiro, Ciro Alberto de
• Format: Article
• Language: English
• Subjects: Brominated compounds; Dioxin; Epithelial-mesenchymal transition; Metalloproteinases; Microvesicles
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2022.120140

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and BDE-209 (decabromodiphenyl ether) are persistent organic pollutants (POPs) produced by industrial activities and associated with several diseases. TCDD is a known human carcinogen, but few studies investigated about the effects of exposure to both compounds, i.e., whether BDE-209 and TCDD can render tumor cells more aggressive and metastatic. In the current study we investigated if the exposure of B16–F1 and B16–F10 melanoma murine cells to environmental relevant concentrations of TCDD and BDE-209 at 24 h and 15-day exposure modulates the expression of genes related to metastasis, making the cells more aggressive. Both pollutants did not affect cell viability but lead to increase of cell proliferation, including the upregulation of vimentin, MMP2, MMP9, MMP14 and PGK1 gene expression and downregulation of E-cadherin, TIMP2, TIMP3 and RECK, strongly suggesting changes in cell phenotypes defined as epithelial to mesenchymal transition (EMT) in BDE-209 and TCDD-exposed cells. Foremost, increased expression of metalloproteinases and decreased expression of their inhibitors made B16–F1 cells similar the more aggressive B16–F10 cell line. Also, the higher secretion of extracellular vesicles by cells after acute exposure to BDE-209 could be related with the phenotype changes. These results are a strong indication of the potential of BDE-209 and TCDD to modulate cell phenotype, leading to a more aggressive profile. [Display omitted] •Low concentrations of BDE-209 and TCDD were non-toxic to B16 cells.•BDE-209 and TCDD exposure increase the expression of invasion-related genes.•BDE-209 and TCD exposure may promote epithelial-mesenchymal transition.