BDE-209 exposure in murine melanoma (B16–F1) cells modulates tumor malignancy and progression in vivo

Abstract

Melanoma is a type of skin cancer considered aggressive due to its high metastatic ability and rapid progression to other tissues and organs. BDE-209 (2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether) is an additive used as a flame retardant and classified as a persistent organic pollutant that has a high bioaccumulation capacity due to its lipophilic nature. This substance has already been detected in rivers, air, soil, plants and even in different human biological samples, such as plasma, umbilical cord blood and breast milk, revealing a great concern to human populations. Thus, in the current study we investigated whether prior exposure of murine melanoma B16–F1 cells to BDE-209 modulates in vivo progression and malignancy of melanoma. B16–F1 cells were cultured and exposed in vitro to BDE-209 (0.01, 0.1 e 1 nM) for 15 days and then inoculated, via caudal vein, in C57BL/6 mice for experimental metastasis analysis after 20 days. Inoculation of BDE-209-exposed cells resulted in 82% increase of metastasis colonized area in the lungs of mice, downregulation of tumor suppressors genes, such as Timp3 and Reck, decrease of lipid peroxidation and increase of systemic and local inflammatory response. These findings are related to melanoma progression. Additionally, the histopathological analysis revealed greater number of focal points of metastases in the lungs and invasiveness of metastases to the mice brain (89%). The results showed that exposure to BDE-209 may alter the phenotype of B16–F1 cells, worsening their metastatic profile. Current data showed that BDE-209 may interfere with the prognosis of melanoma by modulating cells with less invasiveness capacity to a more aggressive profile.