Fear stress enhanced xenograft pancreatic tumor growth through activating epithelial-mesenchymal transition

Objective: Cancer patients often experience multiple emotional distresses, particularly the fear of death. However, there are rare studies to assess the direct effect of the fear of death on disease progression.

Methods: Xenograft pancreatic cancer animal models were established in nude mice. Fear stress was induced to tumor bearing mice by closely housing with a cat and depressive behaviors were measured using open field test, forced swimming test, and sucrose consumption test. Plasma adrenaline concentration was measured using ELISA.

Results: Fear stress induced depression-like behaviors in tumor bearing mice which were accompanied with increases in tumor growth, plasma adrenaline levels as well as the protein expression of alpha 2 adrenergic receptor (α2 AR) and beta 2 adrenergic receptor (β2-AR) in tumor tissues. The β-adrenergic antagonist propranolol (Pro) treatment blocked the effect of stress on tumor growth in pancreatic cancer xenograft animal model, but had no effects on the levels of plasma adrenaline level, and α2 AR and β2-AR expression in tumor tissues. Moreover, fear stress increased Frizzled-1, Wnt1, vimentin, but decreased E-cadherin protein expression in tumor tissues, while Pro reversed the effects of fear stress on the expression of these proteins.

Conclusion: Fear of death impacted the growth of PDAC tumor though activation of epithelial-mesenchymal transition. Treating pancreatic cancer patients with β-adrenergic antagonist implicates an effective strategy to treat cancer including PDAC.