Epidemiological evidence and basic research clearly indicate that stress can affect breast cancer pathogenesis at multiple levels (initiation, tumor growth, and metastasis), although our understanding of the underlying mechanisms is in its infancy. Stress may impair immunosurveillance and can cause persistent inflammation that, during critical life phases, might affect tumor progression. Stress physiology overlaps to a great extent in humans and mice, thus preclinical models can guide and refine hypothesis-driven clinical research questions. In this study we used stressors of different lengths and strengths known to affect neuro-immune functioning to model the diverse experiences of the patients. In a first study we investigated the effect of brief -7 - vs. prolonged -21 days - restraint stress as a risk factor for tumor progression in 4-month-old C57 male mice. Results indicate reduced corticosterone levels on day 7 (short-term stress), followed by an increase on day 21 (long-term procedure). This response was associated with an inverted “U” shape activation of the immune function, with an increase in cytokine levels (TNF-alpha, IL-6 and IL-10) and in hippocampal Brain-Derived Neurotrophic Factor (BDNF) levels. In a second study, gene by environment interactions were studied in a transgenic model of breast cancer (TgNeu). Here we tested the effects of restraint stress in female subjects kept in social isolation for 6 months. This procedure resulted in a more marked immune response in those subjects bearing a genetic susceptibility, TgNeu mice showing greater splenocyte apoptosis, an effect amplified by social isolation and acute stress exposure. Neuroendocrine and histopatological analysis are in progress to assess changes in these parameters. Results from these studies indicate that environmental factors, together with the genetic makeup, can affect susceptibility to tumor progression.
Genetic and environmental factors interact in determining susceptibility to tumor progression: an investigation of neuroendocrine markers in animal models / Francesca Cirulli; Sara Capoccia; Alessandra Berry; Veronica Bellisario; Davide Vacirca; Elena Ortona; Marco Giorgio; Pier Giuseppe Pelicci; Enrico Alleva. - ELETTRONICO. - (2012), pp. 425-425. (Intervento presentato al convegno 8th FENS Forum of Neurosciences tenutosi a Barcellona, Spagna nel 14-18 luglio, 2012).
Genetic and environmental factors interact in determining susceptibility to tumor progression: an investigation of neuroendocrine markers in animal models
CAPOCCIA, SARA;BELLISARIO, VERONICA;
2012
Abstract
Epidemiological evidence and basic research clearly indicate that stress can affect breast cancer pathogenesis at multiple levels (initiation, tumor growth, and metastasis), although our understanding of the underlying mechanisms is in its infancy. Stress may impair immunosurveillance and can cause persistent inflammation that, during critical life phases, might affect tumor progression. Stress physiology overlaps to a great extent in humans and mice, thus preclinical models can guide and refine hypothesis-driven clinical research questions. In this study we used stressors of different lengths and strengths known to affect neuro-immune functioning to model the diverse experiences of the patients. In a first study we investigated the effect of brief -7 - vs. prolonged -21 days - restraint stress as a risk factor for tumor progression in 4-month-old C57 male mice. Results indicate reduced corticosterone levels on day 7 (short-term stress), followed by an increase on day 21 (long-term procedure). This response was associated with an inverted “U” shape activation of the immune function, with an increase in cytokine levels (TNF-alpha, IL-6 and IL-10) and in hippocampal Brain-Derived Neurotrophic Factor (BDNF) levels. In a second study, gene by environment interactions were studied in a transgenic model of breast cancer (TgNeu). Here we tested the effects of restraint stress in female subjects kept in social isolation for 6 months. This procedure resulted in a more marked immune response in those subjects bearing a genetic susceptibility, TgNeu mice showing greater splenocyte apoptosis, an effect amplified by social isolation and acute stress exposure. Neuroendocrine and histopatological analysis are in progress to assess changes in these parameters. Results from these studies indicate that environmental factors, together with the genetic makeup, can affect susceptibility to tumor progression.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.