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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

  • Koual, Meriem1, 2, 3
  • Tomkiewicz, Céline1
  • Guerrera, Ida Chiara4
  • Sherr, David5
  • Barouki, Robert1, 3
  • Coumoul, Xavier1, 3
  • 1 UMR-S1124, Institut national de la santé et de la recherché médicale (Inserm), T3S, Toxicologie Environnementale, Cibles thérapeutiques, Signalisation cellulaire et Biomarqueurs, Paris, France
  • 2 , Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, France , (France)
  • 3 Université de Paris, France , (France)
  • 4 Université de Paris, US24/CNRS UMS3633, Inserm, France , (France)
  • 5 Boston University School of Public Health, USA
Published Article
Environmental Health Perspectives
Environmental Health Perspectives
Publication Date
Mar 08, 2021
DOI: 10.1289/EHP7102
PMID: 33683140
PMCID: PMC7939125
PubMed Central


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.

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