Abstract 4116: Mammary adipocyte-specific metabolic alterations are associated with paracrine effects on mammary tumorigenesis

In rodent models of breast cancer, chronic social stress from isolated housing is associated with increased mammary tumor growth. Interestingly, in several diverse mouse strains, social isolation is also associated with increased expression of the key metabolic genes Acaca, Hk2 and Acly in the adipocyte fraction of the mammary gland. We hypothesized that these gene expression changes would be associated with increased mammary fat glucose metabolism, lipid synthesis, and secretion of paracrine growth promoting adipokines. We found that increased metabolic gene expression in mammary fat did indeed increase both lipid metabolism and leptin secretion from the mammary adipocytes of isolated mice. Surprisingly, visceral fat metabolism and systemic metabolic parameters were unchanged in social isolates, suggesting an effect of social stress that is specific to the mammary fat depot. When mouse mammary cancer cells were treated with culture media derived from the incubation of isolated versus group-housed mouse mammary adipose tissue, the mammary fat secretome of social isolates resulted in significantly increased cancer cell proliferation compared to mammary fat from grouped mice. Current experiments are designed to elucidate the metabolic factors promoting tumor cell proliferation in the mammary fat derived from the stressed animals. We propose a model wherein social isolation and the ensuing heightened neuroendocrine response significantly alters mammary adipocyte metabolism and associated adipokine secretion, thereby potentiating estrogen-independent mammary tumor growth. These studies have implications for understanding the environmental, endocrine, and molecular risk factors associated with estrogen receptor-negative breast cancer. DOD W81XWH-11-1-014901, NIH/NIDDK T32 DK087703, NIH R01CA148814 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4116. doi:1538-7445.AM2012-4116