Psychological Stress and Cancer: New Evidence of An Increasingly Strong Link.
Translational medicine @ UniSa
To date stress, a highly complex process that disrupts homeostasis and involves environmental and psychosocial factors, is considered as one of the most crucial factor that affects our daily life, especially urban dweller's life. Clinical and experimental studies widely support the notion that adrenergic stimulation due to chronic stress affects inflammation and metabolism. In this work, supported by several recent scientific evidences, we show how stress plays a positive role in cancer initiation, progression and cancer metastasis, a negative role for anti-tumor immune function and therapy response. Understanding the intricacies of this interaction could provide an additional help on how act in cancer prevention and therapy.
Stressing Out Cancer: Chronic Stress Induces Dysbiosis and Enhances Colon Cancer Growth.
Cancer research
Psychologic stress significantly impacts colorectal cancer, and chronic stress is known to decrease treatment efficacy and survival rates in patients with colorectal cancer. Previous studies have linked psychologic stress to changes in the gut microbiota, and the role of the microbiota in colorectal cancer progression is well characterized. Despite this, the mechanistic link between chronic stress and colorectal cancer remains unclear. In this issue of Cancer Research, Cao and colleagues reveal that chronic stress exacerbates colorectal cancer progression by reducing the presence of Lactobacillus johnsonii (L. johnsonii) and its metabolite protocatechuic acid (PCA). The authors demonstrate an increase in β-catenin expression as the major mechanism by which chronic stress potentiates cancer stemness and pathogenesis. Administration of L. johnsonii or PCA to stressed mice decreased β-catenin activity and colorectal cancer progression. This study defines a precise mechanism underlying chronic stress and colorectal cancer progression, emphasizing the relevance of psychologic well-being in colorectal cancer outcome. In addition, the study demonstrates the potential efficacy of L. johnsonii or PCA supplementation as promising therapeutics for colorectal cancer treatment. See related article by Cao et al., p. 771.
10.1158/0008-5472.CAN-23-3871
The molecular mechanism of chronic stress affecting the occurrence and development of breast cancer and potential drug therapy.
Liu Hui-Min,Ma Le-le,Li Chunyu,Cao Bo,Jiang Yifang,Han Li,Xu Runchun,Lin Junzhi,Zhang Dingkun
Translational oncology
According to the 2020 data released by the International Agency for Research on Cancer, breast cancer has surpassed lung cancer as the world's most newly diagnosed first-time cancer. Compared with patients with other types of cancer, those with breast cancer experience greater mental stress and more severe psychological impacts because of the life-threatening diagnosis, physical changes, treatment side effects, and family and social life dysfunctions. These usually manifest as anxiety, depression, nervousness, and insomnia, all of which elicit stress responses. Particularly under chronic stress, the continuous release of neurotransmitters from the neuroendocrine system can have a highly profound impact on the occurrence and prognosis of breast cancer. However, because of the complex mechanisms underlying chronic stress and the variability in individual tolerance, evidence of the role of chronic stress in the occurrence and evolution of breast cancer remains unclear. This article reviewed previous research on the correlation between chronic stress and the occurrence and development of breast cancer, particularly the molecular mechanism through which chronic stress promotes breast cancer via neurotransmitters secreted by the nervous system. We also review the progress in the development of potential drugs or blockers for the treatment of breast cancer by targeting the neuroendocrine system.
10.1016/j.tranon.2021.101281
Chronic stress in solid tumor development: from mechanisms to interventions.
Journal of biomedical science
Chronic stress results in disturbances of body hormones through the neuroendocrine system. Cancer patients often experience recurrent anxiety and restlessness during disease progression and treatment, which aggravates disease progression and hinders treatment effects. Recent studies have shown that chronic stress-regulated neuroendocrine systems secret hormones to activate many signaling pathways related to tumor development in tumor cells. The activated neuroendocrine system acts not only on tumor cells but also modulates the survival and metabolic changes of surrounding non-cancerous cells. Current clinical evidences also suggest that chronic stress affects the outcome of cancer treatment. However, in clinic, there is lack of effective treatment for chronic stress in cancer patients. In this review, we discuss the main mechanisms by which chronic stress regulates the tumor microenvironment, including functional regulation of tumor cells by stress hormones (stem cell-like properties, metastasis, angiogenesis, DNA damage accumulation, and apoptotic resistance), metabolic reprogramming and immune escape, and peritumor neuromodulation. Based on the current clinical treatment framework for cancer and chronic stress, we also summarize pharmacological and non-pharmacological therapeutic approaches to provide some directions for cancer therapy.
10.1186/s12929-023-00903-9
Chronic stress-induced immune dysregulation in cancer: implications for initiation, progression, metastasis, and treatment.
American journal of cancer research
Psychological stress is a well-accepted risk factor in cancer initiation and progression. The explosive growth of psychoneuroimmunology research in the past decade has yielded an unprecedented wealth of information about the critical role of chronic stress in the immune dysfunction that influences tumor behaviors, which presents insights to mitigate distress and improve prognosis in cancer patients. Chronic stress exacerbates inflammation and causes a metabolism disorder, making it difficult for the organisms to maintain homeostasis and increasing its susceptibility to cancer. The shifted differentiation and redistribution of the immune system induced by chronic stress fail to combat cancer efficiently. Chronic stress increases the tumor-educated immune suppressive cells and impairs the cytotoxicity of cellular immunity, thereby promoting lymphatic metastasis and hematogenous metastasis. In addition, the efficacy of existing cancer therapies is undermined because chronic stress prevents the immune system from responding properly. Emerging stress-reduction measures have been administered to assist cancer patients to cope with the adverse effects of chronic stress. Here we systematically review the current molecular, cellular, physiological mechanisms about stress-mediated immune responses in the enhancement of tumor initiation and progression, remodeling of tumor microenvironment and impairment of anti-tumor treatment. We also summarize the potential clinically applicable stress-oriented strategies towards cancer and discuss briefly where important knowledge gaps remain.
Psychological Stress and Cellular Aging in Cancer: A Meta-Analysis.
Oxidative medicine and cellular longevity
BACKGROUND:Epidemiological evidence continues to accumulate on the effect of psychosocial and behavioral factors in relation to cancer risk, progression, and mortality. MATERIAL AND METHODS:This article presents the current evidence on the relationship between psychological stress and the risk of cancer and cellular aging process. Ten databases were searched to identify publications up to September 2019. References from retrieved articles were also reviewed. We included nine review papers and 26 cohort or case-control studies based on inclusion/exclusion criteria. RESULTS:Results of previously published review articles did not show consistent evidence for the association between cancer risk and psychological stress, while previous evidence is stronger regarding the role of chronic psychological stress on cancer growth and metastasis and aging. In seven observational studies, severe life events, anxiety, depression, insufficient social support perception, or avoiding coping strategy were significantly associated with breast cancer risk. For other specific types of cancer, 11 studies reported increased risk factors for stressful life events, and two others found increased mortality or a decline in treatment adherence. CONCLUSIONS:Recent epidemiological evidence generally suggests psychosocial factors may be considered risk factors for specific types of cancer and play a key role in the cellular aging process. Understanding molecular mechanisms of the stress interaction is important in cancer management and prevention. The psychological stressors should be considered when developing or evaluating change in psychosocial practice.
10.1155/2019/1270397
Interplay between stress and cancer-A focus on inflammation.
Frontiers in physiology
Stress is an integral part of life. While acute responses to stress are generally regarded as beneficial in dealing with immediate threats, chronic exposure to threatening stimuli exerts deleterious effects and can be either a contributing or an aggravating factor for many chronic diseases including cancer. Chronic psychological stress has been identified as a significant factor contributing to the development and progression of cancer, but the mechanisms that link chronic stress to cancer remain incompletely understood. Psychological stressors initiate multiple physiological responses that result in the activation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system, and the subsequent changes in immune function. Chronic stress exposure disrupts the homeostatic communication between the neuroendocrine and immune systems, shifting immune signaling toward a proinflammatory state. Stress-induced chronic low-grade inflammation and a decline in immune surveillance are both implicated in cancer development and progression. Conversely, tumor-induced inflammatory cytokines, apart from driving a tumor-supportive inflammatory microenvironment, can also exert their biological actions distantly circulation and therefore adversely affect the stress response. In this minireview, we summarize the current findings on the relationship between stress and cancer, focusing on the role of inflammation in stress-induced neuroendocrine-immune crosstalk. We also discuss the underlying mechanisms and their potential for cancer treatment and prevention.
10.3389/fphys.2023.1119095
Psychosocial Stress and Age Influence Depression and Anxiety-Related Behavior, Drive Tumor Inflammatory Cytokines and Accelerate Prostate Cancer Growth in Mice.
Bellinger Denise L,Dulcich Melissa S,Molinaro Christine,Gifford Peter,Lorton Dianne,Gridley Daila S,Hartman Richard E
Frontiers in oncology
Prostate cancer (PCa) prevalence is higher in older men and poorer coping with psychosocial stressors effect prognosis. Yet, interactions between age, stress and PCa progression are underexplored. Therefore, we characterized the effects of age and isolation combined with restraint (2 h/day) for 14 days post-tumor inoculation on behavior, tumor growth and host defense in the immunocompetent, orthotopic RM-9 murine PCa model. All mice were tumor inoculated. Isolation/restraint increased sympathetic and hypothalamic-pituitary-adrenal cortical activation, based on elevated serum 3-methoxy-4-hydroxyphenylglycol/norepinephrine ratios and corticosterone levels, respectively. Elevated zero maze testing revealed age-related differences in naïve C57Bl/6 mice, and increased anxiety-like behavior in tumor-bearing mice. In open field testing, old stressed mice were less active throughout the 30-min test than young non-stressed and stressed, and old non-stressed mice, suggesting greater anxiety in old stressed mice. Old (18 month) mice demonstrated more depression-like behavior than young mice with tail suspension testing, without effects of isolation/restraint stress. Old mice developed larger tumors, despite similar tumor expression of tumor vascular endothelial growth factor or transforming growth factor-beta1 across age. Tumor chemokine/cytokine expression, commonly prognostic for poorer outcomes, were uniquely age- and stress-dependent, underscoring the need for PCa research in old animals. Macrophages predominated in RM-9 tumors. Macrophages, and CD4 and CD4FoxP3 T-cell tumor infiltration were greater in young mice than in old mice. Stress increased macrophage infiltration in old mice. Conversely, stress reduced intratumoral CD4 and CD4FoxP3 T-cell numbers in young mice. CD8 T-cell infiltration was similar across treatment groups. Our findings support that age- and psychological stress interacts to affect PCa outcomes by interfering with neural-immune mechanisms and affecting behavioral responses.
10.3389/fonc.2021.703848
Chronic Unpredictable Mild Stress Accelerates the Growth of Bladder Cancer in a Xenograft Mouse Model.
Zhou Qidong,Ding Weihong,Qian Zhiyu,Jiang Guangliang,Sun Chuanyu,Xu Ke
Psychology research and behavior management
Objective:Chronic psychological stress is common in patients with bladder cancer. An increasing number of evidence demonstrated that psychiatric disorder leads to worse prognostic outcomes in bladder cancer. This study was to investigate the effects of chronic psychological stress on the growth of bladder cancer and its potential mechanisms. Methods:A xenograft mouse model was established by subcutaneously implanting the human bladder cancer cell line T24 into nude mice. All of the tumor-bearing mice (N=20) were randomly separated into two groups. Mice in the control group were subjected to normal feeding conditions, while in another group, a chronic unpredictable mild stress (CUMS) model was established, in which mice were exposed to various types of stressors. Various analyses were performed on parameters including the tumor volume, tumor weight, expression of Caspase-3 and VEGF, proportion of Ki-67 positive cells (Ki-67 index), microvessel density (MVD) and serum concentrations of epinephrine and cortisol. Results:In the CUMS group, the growth of transplanted tumors was distinctly accelerated, with the weight of removed tumors at the end of experiment increased by 34.07% compared to that of the control. Serum levels of epinephrine and cortisol determined by ELISA were significantly increased by CUMS. Immunohistochemistry and Western blot analysis showed that the expression of Caspase-3 was downregulated, whereas the expression of VEGF was upregulated in the CUMS group. Meanwhile, CUMS could increase the Ki-67 index and MVD. Conclusion:Our research supports the hypothesis that CUMS could affect the growth of bladder cancer in nude mice, indicating that the intervention of chronic psychological stress may be a possible therapeutic strategy for bladder cancer.
10.2147/PRBM.S288983
Investigating the crosstalk between chronic stress and immune cells: implications for enhanced cancer therapy.
Frontiers in neuroscience
Chronic stress has a substantial influence on the tumor microenvironment (TME), leading to compromised effectiveness of anti-cancer therapies through diverse mechanisms. It disrupts vital functions of immune cells that play a critical role in anti-tumor immunity, such as the inhibition of dendritic cells (DCs) and lymphocytes, while simultaneously enhancing the activity of immune cells that support tumor growth, such as myeloid-derived suppressor cells and tumor-associated macrophages. Furthermore, chronic stress exerts a significant impact on crucial mechanisms within the TME, including angiogenesis, DNA repair, hypoxia, extracellular matrix deposition, and tumor metabolism. These alterations in the TME, induced by stress, result from the activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, in conjunction with epigenetic modifications. In conclusion, chronic stress significantly influences the TME and impedes the efficacy of anti-cancer treatments, underscoring the importance of targeting stress pathways to improve therapeutic results.
10.3389/fnins.2023.1321176