Cigarette smoke and tumor microenvironment copromote aggressiveness of human breast cancer cells

• Published in: Toxicological sciences Vol. 192; no. 1; pp. 30 - 42
• Main Authors: Benoit, Louise, Tomkiewicz, Celine, Delit, Maxime, Khider, Hanna, Audouze, Karine, Kowandy, Flavie, Bortoli, Sylvie, Barouki, Robert, Coumoul, Xavier, Koual, Meriem
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 20.03.2023
• Subjects: Breast - metabolism; Breast Neoplasms - metabolism; Cigarette Smoking; Epithelial-Mesenchymal Transition; Female; Humans; MCF-7 Cells; Tumor Microenvironment; mammary cancer; adipose tissue; metastasis; pollutants; smoking
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfad013

Abstract Breast cancer is a major public health issue and the role of pollutants in promoting breast cancer progression has recently been suggested. We aimed to assess if a mixture of pollutants, cigarette smoke, could favor the aggressivity of breast cancer cells. We also evaluated the impact of the tumor microenvironment, largely represented by adipocytes, in mediating this modification of cell phenotype. Breast cancer cells lines, MCF-7 were cultured using a transwell coculture model with preadipocytes hMADS cells or were cultured alone. Cells were treated with cigarette smoke extract (CSE) and the four conditions: control, treated by CSE, coculture, and coexposure (coculture and CSE) were compared. We analyzed morphological changes, cell migration, resistance to anoikis, stemness, epithelial-to-mesenchymal transition (EMT), and the presence of hormonal receptors in each condition. A complete transcriptomic analysis was carried out to highlight certain pathways. We also assessed whether the aryl hydrocarbon receptor (AhR), a receptor involved in the metabolism of xenobiotics, could mediate these modifications. Several hallmarks of metastasis were specific to the coexposure condition (cell migration, resistance to anoikis, stemness characterized by CD24/CD44 ratios and ALDH1A1 and ALDH1A3 rates) whereas others (morphological changes, EMT, loss of hormonal receptors) could be seen in the coculture condition and were aggravated by CSE (coexposure). Moreover, MCF-7 cells presented a decrease in hormonal receptors, suggesting an endocrine treatment resistance. These results were confirmed by the transcriptomic analysis. We suggest that the AhR could mediate the loss of hormonal receptor and the increase in cell migration