Mice housed in an enriched environment (EE) have inhibited tumor development because of eustress (positive stress) stimulation. However, the mechanisms underlying increased cancer resistance in EEs remain unclear; this may be due to poor reproducibility of the results because of the complicated EE assembly requirements. In this study, we examined the effects of a simplified EE (sEE) model, consisting only of a nesting shelter and a running wheel, on cancer development in mice. We found that, similar to the complex EE, the sEE promoted motor function and alleviated anxiety in mice. Moreover, the mice housed in the sEE showed inhibited tumor growth and metastasis in addition to a higher average body temperature (especially at the point of transition from light to darkness). Furthermore, mice in the sEE had a decreased brown adipose tissue (BAT) mass, with a significant upregulation of the Ucp1 and Adrb3 genes (which encode uncoupling protein 1 and β-adrenergic receptor, respectively) observed in the BAT at the point of transition from light to darkness. An antibody against the immune checkpoint protein programmed cell death 1 was also found to have an additive effect with the sEE against tumor development. Our findings indicate that the established sEE model may be a useful tool for studying the antitumor effects of eustress and can potentially introduce new avenues for cancer prevention and treatment.
Keywords: animal models of cancer; body temperature; cancer prevention; enriched environment; eustress.