Stress is a risk factor for tumor progression: investigation on neuroendocrine and immune biomarkers

The sustained activation of the hypothalamic-pituitary-adrenal (HPA) axis and the consequent suppression of the immune function, mediated by glucocorticoid (GCs) hormones, can render vulnerable individuals more susceptible to neoplastic processes. In this regard Brain-Derived Neurotrophic Factor (BDNF) may represent a crucial factor for the integration of neural, immune, endocrine and metabolic responses to stressful challenges, including tumor progression. In a first study we investigated the effect of brief (7 days) vs. prolonged (21 days) restraint in C57 male mice. Results show reduced corticosterone levels after 7 days of stress procedure, associated with an increase in cytokine (TNF-alpha, IL-6 and IL-10) as well as in hippocampal BDNF levels. In a second study, a mouse model of breast cancer (TgNeu), underwent a combination of environmental stressors in order to characterize gene by environment interaction. In particular, we tested the effects of restraint stress in female subjects previously isolated from their conspecifics for 6 months. TgNeu mice showed greater splenocyte apoptosis an effect amplified by social isolation and acute stress exposure. In addition TgNeu mice were characterized by increased basal hippocampal BDNF levels that showed a sharp decrease following restraint stress. Neuroendocrine and epigenetic studies are in progress. Overall, results indicate that environmental factors can contribute, together with the genetic makeup, to determine susceptibility to tumor onset and progression.