Chronic Stress Promotes Epithelial-Mesenchymal Transition in Lung Carcinogenesis Through the Induction of TGF-1

Background and Objective: Chronic stress promotes tumor progression but the specific mechanism in the sympathetic nervous system is unclear. To explore the mechanism of whether chronic stress affects hormone levels and thus tumor progression, this study was conducted. Materials and Methods: A tumor-bearing mouse model was constructed by inoculating tumor cells and depression-like phenotype by chronic unpredictable mild stress, CUMS. The A549 cells were exposed to stress hormones. Mice were divided into 4 groups (n = 8): Control group, Tumor group, CUMS group and Tumor+CUMS group. Detecting the changes of mice models of tumor, CUMS and Tumor+CUMS in serum hormone and molecules of epithelial-mesenchymal transformation (EMT) in tumor tissues. The change of molecules of EMT when exposing A549 cells to cortisol and norepinephrine. Results: Chronic stress led to the increase of serum corticosterone and noradrenaline and enhanced the metastasis and invasion of cancer cells. In vivo chronic stress resulted in increased expression of tumor TGF-beta 1 and the changes of EMT-related molecules were also consistent with its course. In vitro, A549 cells showed morphological changes under CORT and NE, enhanced cloning, migration and invasion ability, up-regulated the expressions of TGF-beta 1, N-cadherin and Vimentin, down-regulated E-cadherin and ZO-1. The opposite phenomenon occurred after knocking down TGF-beta 1. However, CORT and NE reversed these changes. Conclusion: The high stress hormone levels caused by chronic stress affected the expression of TGF-beta 1 and thus promoted the tumor EMT.