Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment

Figure 7

Combined stimulation by TNFα + Estrogen + EGF leads to acquisition of mesenchymal phenotype by the tumor cells, and to upregulation of EMT inducers. Breast tumor cells were stimulated by TNFα + Estrogen + EGF (concentrations as in Figure 1) for three days. Non-stimulated: cells grown with the diluents of the above factors. (a) Cell morphology was determined by light microscopy at ×20 magnification. (a1) Non-stimulated cells. (a2) Cells stimulated by TNFα + Estrogen + EGF. Arrows point to some of the cells that have undergone remodeling in response to TNFα + Estrogen + EGF stimulation. In all panels, the results are from a representative experiment of 𝑛≥3. (b) Expression of the EMT inducers Zeb1, Snail, and Slug in cells stimulated by TNFα + Estrogen + EGF and in non-stimulated cells (grown with the diluents of the factors), determined by qPCR analysis. In all panels, the results are from a representative experiment of 𝑛≥3.