S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells

Abstract To understand the potential effects of cancer cells on surrounding normal mammary epithelial cells, we performed direct co-culture non-tumorigenic MCF10A and various breast cells. Firstly, observed dynamic cell–cell interactions between including lamellipodia or nanotube-like contacts transfer extracellular vesicles. Co-cultured exhibited features epithelial-mesenchymal transition, showed increased capacity cell proliferation, migration, colony formation, 3-dimensional sphere formation. Direct most distinct phenotype changes in followed by conditioned media treatment indirect co-culture. Transcriptome analysis phosphor-protein array suggested that several cancer-related pathways are significantly dysregulated after with S100A8 S100A9 up-regulation co-cultured their microenvironmental upregulation was also orthotropic xenograft syngeneic mouse tumors. When S100A8/A9 overexpression induced phenotypic directly terms vitro behaviors signaling activities suggesting a S100A8/A9-mediated transition program This study suggests possibility could lead to substantial molecular functional characteristics