Oncostatin-M promotes phenotypic changes associated with mesenchymal and stem cell-like differentiation in breast cancer

Cancer stem cell (CSC) biology and the epithelial-to-mesenchymal transition (EMT) are thought to be mechanistically linked and may be key components of cancer development and progression. However, stimuli that induce EMT and CSC-like features ('stemness') are poorly defined. We and others have shown that the inflammatory cytokine oncostatin-M (OSM) mediates phenotypic changes in breast cancer that are consistent with EMT and dedifferentiation, including enhanced migration and loss of hormone receptors. In this study, we have expanded on these prior observations to determine whether OSM is a cell-extrinsic driver of EMT and/or stemness. OSM stimulation of the luminal breast cancer cell lines MCF7 and T47D induced EMT features including loss of membranous E-cadherin and induction of snail and slug expression. OSM treatment markedly enhanced the formation of mammospheres (up to 20-fold, P