Social stress is associated with altered mammary adipocyte metabolism in a model of triple negative breast cancer.

摘要

Although the association between cancer biology and obesity is well-established, and adipose tissue is now widely accepted as an endocrine organ, the mechanisms by which secreted proteins and/or metabolites from adipose tissue contribute to cancer biology are not well understood. Equally inadequately understood is how social stress affects cancer biology. We know that the neuroendocrine system links behavior and experience with adrenal hormone secretion and subsequent gene expression changes, thereby connecting the human stress response to disease susceptibility. The principal theme underlying the scientific understanding of chronic, unrelenting stress (rather than an acute stressor) is that it appears to elicit a maladaptive physiological response. Thus, chronic stress is associated with a variety of human pathologies including cardiovascular disease and cancer. Within modern societies, perhaps the most prevalent chronic stressor, social isolation and its ensuing lack of social support, appear to disproportionately plague minority groups and the poor. Epidemiological evidence suggests that the effects of social isolation on marginalized populations result in differing breast cancer biology and worse overall outcome following breast cancer diagnosis. In this dissertation, a relationship between exposure to social isolation, altered mammary adipose tissue metabolism, and breast cancer progression is detailed. Evidence for a unique neuroendocrine-response regulating lipid synthesis specifically in mammary adipocytes is provided, along with data implicating lysophospholipids as important mammary adipocyte-derived metabolites that signal to cancer cells. Together, these investigations lay a foundation for detailed in vivo studies into the relationship between social stress, altered mammary adipocyte lipid metabolism, and breast cancer progression.