The influence of glucocorticoid signaling on tumor progression

Abstract

The diagnosis of cancer elicits a broad range of well-characterized stress-related biobehavioral responses. Recent studies also suggest that an individual's neuroendocrine stress response can influence tumor biology. One of the major physiological pathways altered by the response to unrelenting social stressors is the hypothalamic-pituitary-adrenal or HPA axis. Initially following acute stress exposure, an increased glucocorticoid response is observed; eventually, chronic stress exposure can lead to a blunting of the normal diurnal cortisol pattern. Interestingly, recent evidence also links high primary tumor glucocorticoid receptor expression (and associated increased glucocorticoid-mediated gene expression) to more rapid estrogen-independent breast cancer progression. Furthermore, animal models of human breast cancer suggest that glucocorticoids inhibit tumor cell apoptosis. These findings provide a conceptual basis for understanding the molecular mechanisms underlying the influence of the individual's stress response, and specifically glucocorticoid action, on breast cancer and other solid tumor biology. How this increased glucocorticoid signaling might contribute to cancer progression is the subject of this review.

Fig. 1

The multi-layered environments of tumor growth within an individual. The malignant cell environment exists within a nested series of environments capable of varying levels of reciprocal communication. The stressors and support systems of an individual’s social environment (dark gray) can interact with an individuals psychological environment (dark pink) to impact the physiology of the systemic environment (pale gray). These physiological changes can promote tumor progression by directly affecting tumor biology or indirectly though the microenvironment (pale pink). Transdisciplinary research considers all five environments through the coordinated experiments of both social and biological scientists using unifying model systems.