Human adipose-derived mesenchymal stem cells promote breast cancer MCF7 cell epithelial-mesenchymal transition by cross interacting with the TGF-/Smad and PI3K/AKT signaling pathways

The influence and underlying mechanisms of human adipose-derived stem cells (Hu-ADSCs) on breast cancer cells in the tumor microenvironment remain unclear. Understanding the association between Hu-ADSCs and cancer cells may provide targets for breast cancer treatment and reference for the clinical application of stem cells. Therefore, a Hu-ADSC and breast cancer MCF7 cell coculture system was established to investigate the paracrine effects of Hu-ADSCs on MCF7 cell migration and invasion, in addition to the potential mechanism of action by reverse transcription-quantitative polymerase chain reaction and western blotting. Hu-ADSCs enhanced MCF7 cell migration and invasion by decreasing the expression of epithelial marker E-cadherin, and increasing the expression of interstitial marker N-cadherin and epithelial-mesenchymal transition (EMT) transcription factors in vitro. The EMT effect of cocultured MCF7 cells was inhibited with the addition of anti-transforming growth factor (TGF)-1 or phosphoinositide 3-kinase (PI3K) inhibitor LY294002, accompanied by a significant decrease in phosphorylated (p)-mothers against decapentaplegic homolog (Smad) and p-protein kinase B (AKT) expression. The data suggested that the paracrine effect of Hu-ADSCs in the tumor microenvironment promoted the EMT of MCF7 cells by cross interacting with the TGF-/Smad and PI3K/AKT pathways.