Aggressiveness and metastatic potential of breast cancer cells co-cultured with preadipocytes and exposed to an environmental pollutant dioxin: An in vitro and in vivo zebrafish study

Abstract

BACKGROUND: Breast cancer (BC) is a major public health concern, and its prognosis is very poor once metastasis occurs. The tumor microenviron-ment and chemical pollution have been suggested recently to contribute, independently, to the development of metastatic cells. The BC microenviron-ment consists, in part, of adipocytes and preadipocytes in which persistent organic pollutants (POPs) can be stored. OBJECTIVES: We aimed to test the hypothesis that these two factors (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an extensively studied, toxic POP and the microenvironment) may interact to increase tumor aggressiveness. METHODS: We used a co-culture model using BC MCF-7 cells or MDA-MB-231 cells together with hMADS preadipocytes to investigate the contri-bution of the microenvironment and 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD on BC cells. Global differences were characterized using a high-throughput proteomic assay. Subsequently we measured the BC stem cell–like activity, analyzed the cell morphology, and used a zebrafish larvae model to study the metastatic potential of the BC cells. RESULTS: We found that coexposure to TCDD and preadipocytes modified BC cell properties; moreover, it induced the expression of ALDH1A3, a cancer stem cell marker, and the appearance of giant cancer cells with cell-in-cell structures (CICs), which are associated with malignant metastatic progression, that we demonstrated in vivo. DISCUSSION: The results of our study using BC cell lines co-cultured with preadipocytes and a POP and an in vivo zebrafish model of metastasis sug-gest that the interactions between BC cells and their microenvironment could affect their invasive or metastatic potential. https://doi.org/10.1289/EHP7102.