PMID- 33683140 OWN - NLM STAT- MEDLINE DCOM- 20211125 LR - 20220531 IS - 1552-9924 (Electronic) IS - 0091-6765 (Print) IS - 0091-6765 (Linking) VI - 129 IP - 3 DP - 2021 Mar TI - 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. PG - 37002 LID - 10.1289/EHP7102 [doi] LID - 037002 AB - BACKGROUND: Breast cancer (BC) is a major public health concern, and its prognosis is very poor once metastasis occurs. The tumor microenvironment and chemical pollution have been suggested recently to contribute, independently, to the development of metastatic cells. The BC microenvironment 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 contribution 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 suggest that the interactions between BC cells and their microenvironment could affect their invasive or metastatic potential. https://doi.org/10.1289/EHP7102. FAU - Koual, Meriem AU - Koual M AD - UMR-S1124, Institut national de la sante et de la recherche medicale (Inserm), T3S, Toxicologie Environnementale, Cibles therapeutiques, Signalisation cellulaire et Biomarqueurs, Paris, France. AD - Service de Chirurgie Cancerologique Gynecologique et du Sein, Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, France. AD - Universite de Paris, Paris, France. FAU - Tomkiewicz, Celine AU - Tomkiewicz C AD - UMR-S1124, Institut national de la sante et de la recherche medicale (Inserm), T3S, Toxicologie Environnementale, Cibles therapeutiques, Signalisation cellulaire et Biomarqueurs, Paris, France. FAU - Guerrera, Ida Chiara AU - Guerrera IC AD - Plateforme proteomique 3P5-Necker, Structure Federative de Recherche Necker, Universite de Paris, US24/CNRS UMS3633, Inserm, Paris, France. FAU - Sherr, David AU - Sherr D AD - Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA. FAU - Barouki, Robert AU - Barouki R AD - UMR-S1124, Institut national de la sante et de la recherche medicale (Inserm), T3S, Toxicologie Environnementale, Cibles therapeutiques, Signalisation cellulaire et Biomarqueurs, Paris, France. AD - Universite de Paris, Paris, France. FAU - Coumoul, Xavier AU - Coumoul X AD - UMR-S1124, Institut national de la sante et de la recherche medicale (Inserm), T3S, Toxicologie Environnementale, Cibles therapeutiques, Signalisation cellulaire et Biomarqueurs, Paris, France. AD - Universite de Paris, Paris, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210308 PL - United States TA - Environ Health Perspect JT - Environmental health perspectives JID - 0330411 RN - 0 (Dioxins) RN - 0 (Environmental Pollutants) RN - 0 (Polychlorinated Dibenzodioxins) SB - IM MH - Animals MH - *Breast Neoplasms/chemically induced MH - Coculture Techniques MH - *Dioxins MH - *Environmental Pollutants MH - Female MH - Humans MH - MCF-7 Cells MH - *Polychlorinated Dibenzodioxins MH - Proteomics MH - Tumor Microenvironment MH - Zebrafish PMC - PMC7939125 EDAT- 2021/03/09 06:00 MHDA- 2021/11/26 06:00 PMCR- 2021/03/08 CRDT- 2021/03/08 12:12 PHST- 2021/03/08 12:12 [entrez] PHST- 2021/03/09 06:00 [pubmed] PHST- 2021/11/26 06:00 [medline] PHST- 2021/03/08 00:00 [pmc-release] AID - EHP7102 [pii] AID - 10.1289/EHP7102 [doi] PST - ppublish SO - Environ Health Perspect. 2021 Mar;129(3):37002. doi: 10.1289/EHP7102. Epub 2021 Mar 8.