Abstract PL01-04: Stress and the social environment: Impact on cancer risk
Authors: Conzen Suzanne 
Published: January 2014

The breast cancer research community has long considered the impact of exogenous estrogen exposure, nutrition, alcohol consumption, and exercise on breast cancer biology. More recently, experimental studies of exposure to chronic stressors in the social environment and the resulting stress response have suggested that epinephrine- and glucocorticoid-mediated signaling pathways might potentiate breast cancer growth both at primary and metastatic tumor sites. To study this hypothesis in more detail, we initiated a transdisciplinary study of a well-established social stressor for female rodents- chronic social isolation. We found that exposing a young female rodent to chronic socially isolation for 12 weeks (compared to group living/social interaction with three other female mice) was associated with increased mammary tumor growth in genetically predisposed rodents. For example, in the C3(1)/SV40 T-antigen (Tag) FVB/N mouse model of “triple-negative” (ER,PR and ErbB-negative breast cancer) the heightened stress response elicited by chronic social isolation was associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e. during the in situ carcinoma stage when the animals are 15 weeks of age). This suggested that metabolic changes within the mammary gland could affect breast cancer biology.

To further understand how accelerated mammary tumor growth may be associated with the physiological response to social isolation, we separated the mammary gland adipose tissue from its adjacent ductal epithelial cells and then analyzed individual cell types for changes in metabolic gene expression. We found that the major increase in expression of the key metabolic genes Acaca, Hk2 and Acly was primarily in the adipocyte (fat cell) fraction of the mammary gland. In contrast, metabolic gene expression was not significantly increased in visceral or gonadal adipose depots of socially isolated female mice, suggesting that the stress response affects individual fat depots differently in this model. We confirmed that the increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and local leptin production; interestingly, systemic leptin levels were not significantly altered. Furthermore, compared to the group housed mammary fat, application of media that had been cultured with isolated mouse mammary adipose tissue resulted in relatively increased proliferation of mammary cancer cells. These results suggest that the physiological response to a chronic social stressor (isolation) results in metabolic changes in mammary gland adipocytes that in turn contribute to increased proliferation of pre-invasive malignant epithelial cells. Adipocyte-secreted metabolites and/or tumor growth-promoting proteins could identify biomarkers and/or targets for preventive intervention in breast cancer. We are currently examining the mammary fat of the isolated versus group-housed mice to identify differential production of adipokines and lipid species that may influence early breast cancer growth in this model.

Citation Format: Suzanne Conzen. Stress and the social environment: Impact on cancer risk. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr PL01-04.