Effect of chronic stress on tumorigenesis and development

Abstract

Chronic stress activates the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis to aggravates tumorigenesis and development. Although the importance of SNS and HPA in maintaining homeostasis has already attracted much attention, there is still a lot remained unknown about the molecular mechanisms by which chronic stress influence the occurrence and development of tumor. While some researches have already concluded the mechanisms underlying the effect of chronic stress on tumor, complicated processes of tumor progression resulted in effects of chronic stress on various stages of tumor remains elusive. In this reviews we concluded recent research progresses of chronic stress and its effects on premalignancy, tumorigenesis and tumor development, we comprehensively summarized the molecular mechanisms in between. And we highlight the available treatments and potential therapies for stressed patients with tumor.

Keywords: Epinephrine; Glucocorticoids; Norepinephrine; Tumor formation; Tumor inhibition; Tumor progression.

Fig. 1

SNS and HPA axis regulates organs and tissues under stress. Under stressor, catecholamine and glucocorticoid releasing from SNS synapse, adrenal medulla and adrenal cortex play a dominant role in the regulation of stress response. SNS can manipulate almost all physiological functions of various organs including breast, liver, stomach and intestines. While HPA axis regulate metabolic and inflammatory effects through glucocorticoid

Fig. 2

Regulating mechanisms of chronic stress. Upon stimulation of stressor, catecholamine and glucocorticoid releasing from SNS synapse, adrenal medulla and adrenal cortex play a dominant role in the regulation of stress response. SNS can manipulate almost all physiological functions of various organs including breast, liver, stomach and intestines. While HPA axis regulate metabolic and inflammatory effects

Fig. 3

Effects of chronic stress on tumor microenvironment. a Catecholamine and glucocorticoids accelerate tumorigenesis through promoting DNA damage, gene mutation and preventing tumor cells from autophagy and apoptosis. b Chronic stress promotes the premalignancy such as liver fibrosis and inflammatory bowel diseases through releasing IL-6 and IL-8. c Tumor cells in the microenvironment can be transformed into cancer stem cells(CSCs). d Chronic stress can suppress the anti-tumor immunity response through decreasing the numbers of cytotoxic T cells, dendritic cells(DCs),Natural Killer cells(NK cells) and increasing regular T cells and myeloid-derived suppression cells (MDSCs). e Chronic stress enhances the releasing of inflammatory factors including IL-6 and IL-8 and increases the number of monocytes to facility the inflammation. f Chronic stress advances tumor migration and metastasis via increasing the migration capability of tumor cells, regulating angiogenesis and lymphangiogenesis and promoting the formation of tumor microenvironment