Cigarette smoke and tumor micro-environment co-promote aggressiveness of human breast cancer cells

Abstract The role of the environment in breast cancer (BC) progression has recently been suggested. We aimed to assess if a mixture of pollutants, cigarette smoke, could favor its aggressivity. We also evaluated the impact of the micro-environment, largely represented by adipocytes, in mediating this.BC cells lines MCF-7 were cultured using a transwell co-culture model with preadipocytes hMADS cells or were cultured alone. Cells were treated by cigarette smoke extract (CSE) and the four conditions: control, CSE, co-culture and co-exposure (co-culture and CSE) were compared. We analyzed morphological changes, cell migration, resistance to anoikis, stemness, epithelial to mesenchymal transition (EMT) and presence of hormonal receptors in each condition. A complete transcriptomic analysis was carried out to highlight certain pathways.Several hallmarks of metastasis were specific to the coexposure condition (cell migration, resistance to anoikis, stemness) 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. Our in vitro results suggest that a common mixture of pollutants could promote BC metastasis in a co-culture model.