
Chronic stress promotes gastric cancer progression via the adrenoceptor beta 2/PlexinA1 pathway.
Cell stress & chaperones
Chronic stress is a common emotional disorder in cancer patients. Chronic stress promotes progression of gastric cancer (GC) and leads to poor outcomes. However, the underlying mechanisms remain not clear. Herein, we explored the possible mechanisms of chronic stress in GC progression. The Cancer Genome Atlas (TCGA) datasets were analyzed for differentially expressed genes. Clinical data of GC were evaluated for their association with PlexinA1 using TCGA and Kaplan-Meier-plotter databases. Chronic stress of GC patients was evaluated using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Chronic unpredictable mild stress (CUMS) was used to induce chronic stress in mice. Gastric xenograft tumor was constructed using the sewing method. Chronic stress-like behaviors were assessed using light/dark box and tail suspension tests. Protein expression was detected using immunohistochemistry and Western blot analysis. Analyses of TCGA and the Kaplan-Meier-plotter databases showed that patients with high levels of PlexinA1 in GC had worse overall survival than those with low levels of PlexinA1. A total of 36 GC patients were enrolled in the study, and about 33% of the patients had chronic stress. Compared with patients without chronic stress, higher expression levels of adrenoceptor beta 2 and PlexinA1 were observed in patients with chronic stress. The tumor size in mice under CUMS was significantly increased compared with the control mice. Adrenoceptor beta 2, PlexinA1, N-cadherin, and alpha-smooth muscle actin, as well as Ki67 were highly expressed in the tumors of CUMS group. However, E-cadherin was lowly expressed in the tumors of CUMS group. Importantly, chemical sympathectomy with 6-hydroxydopamine or treatment with a selective β2 adrenergic receptor antagonist (ICI118,551) could reverse these effects. Our findings suggest that chronic stress plays an important role in GC progression and there is a potential for blocking the epinephrine-β2AR/PlexinA1 pathway in the treatment of GC.
10.1016/j.cstres.2024.02.001
The relation between stressful life events and breast cancer: a systematic review and meta-analysis of cohort studies.
Bahri Narjes,Fathi Najafi Tahereh,Homaei Shandiz Fatemeh,Tohidinik Hamid Reza,Khajavi Abdoljavad
Breast cancer research and treatment
PURPOSE:Breast cancer is the most common cancer among women with high rate of mortality. This systematic review and meta-analysis was conducted to investigate the relation between stressful life events and breast cancer. METHODS:We searched PubMed, Scopus, ScienceDirect, and Google scholar databases from their inception until June 2018. The keywords and phrases we used in the search were (life events AND stress AND breast cancer OR neoplasm) to identify potentially relevant cohort studies that reported relative risk estimates and confidence intervals of this association. Pooled Risk ratio and 95% confidence intervals (CIs) were calculated using random effects model. RESULTS:Out of 168 potentially relevant publications, 11 documents met the inclusion criteria. The results showed that history of stressful life events slightly increases the risk of breast cancer [pooled Risk Ratio: 1.11 (95% CI 1.03 to 1.19)]. CONCLUSIONS:History of stressful life events could be associated with a moderate increase in the risk of breast cancer. We advise that receiving psychological and counseling services after occurrence of stressful life events of women should be taken seriously.
10.1007/s10549-019-05231-x
Associations between experience of stressful life events and cancer prevalence in China: results from the China Kadoorie Biobank study.
BMC cancer
BACKGROUND:Studies examining the relationships of stressful life events and cancer yielded inconsistent findings, while relevant evidence in mainland China is scarce. The current study sought to determine whether experience of stressful life events was associated with cancer prevalence in Chinese population. METHODS:We used cross-sectional data from the China Kadoorie Biobank study which that recruited 0.5 million Chinese adults aged 30 to 79 from 2004 to 2008. Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cancer associated with stressful life events reported at baseline. RESULTS:Among the 461,696 participants included in this analysis, 2,122 (0.46%) had self-reported cancer with the mean (SD) age was 57.12 (9.71) years. Compared to those without any stressful life event, participants who experienced 1 and 2 or more events had significantly higher odds of cancer, with the ORs of 1.80 (95% CI: 1.58-2.05) and 3.05 (2.18-4.28). For categories of work-, family-, and personal-related events, the OR of cancer was 1.48 (1.07-2.05), 2.06 (1.80-2.35), and 1.65 (1.17-2.33), respectively. Regarding the specific stressful life events, loss of income/living on debt, major conflict within family, death/major illness of other close family member, and major injury/traffic accident were significantly associated with increased odds of cancer, with the ORs of 2.64 (1.81-3.86), 1.73 (1.20-2.50), 2.36 (2.05-2.72), and 2.11 (1.43-3.13). CONCLUSION:Our findings suggested that experiences of cumulative and specific stressful life events were significantly associated with increased cancer prevalence in Chinese population.
10.1186/s12885-023-11659-8
Increased Levels of Stress Induces a More Metastatic Phenotype in Human Melanoma Cells.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Growing evidence suggests that stress plays a vital role in metastasis and tumor development by activating the sympathetic nervous system. The catecholamines released into the tumor microenvironment (TME), specifically norepinephrine (NE), results in a cascade effect leading to a variety of pro-metastatic activities that sustain tumor growth and increase melanoma aggressiveness. Most notable are the secretion of cytokines and the stimulation of tumor-associated macrophages (TAMs). Using a co-culture system of several human melanoma cancer cells and macrophages, we found that sustained exposure of NE in the TME induced the release of tumor-growth and progression-associated cytokines from TAMs. Several of the upregulated cytokines found, including IL-11, IL-24, GRO-a, MIF, DKK-1, and angiopoietin-2, are known to induce growth, migration, invasion, and tumor development in human melanoma. An ELISA assay of human-MIF was used to validate the cytokine array in which upregulation of MIF was noted in co-culture with NE present. At a molecular level, these findings suggest how physiological stress in cancer patients can further lead to cancer progression. These preliminary findings may lead to supportive therapies that emphasize mental health and the treatment of the psychological state of the patient. Our next steps include continuing the validation of the cytokine arrays using different ELISA assays to quantify protein levels of stress-secreted cytokines in the TME that augment the metastatic phenotype of human melanoma cells.
10.1096/fasebj.2022.36.S1.R5234
The Role of Psychologic Stress in Cancer Initiation: Clinical Relevance and Potential Molecular Mechanisms.
Cancer research
The hypothesis that the physiologic response to psychologic stress influences the initiation of cancer is highly controversial. The link between initiating stressors, the psychologic stress response, and disease is plausible, considering that the stress response is associated with defined physiologic outcomes and molecular mechanisms. In light of this, we review the clinical relevance of psychologic stress on the risk of cancer, and we propose potential molecular pathways that may link the stress response to early stages of malignant cell transformation.
10.1158/0008-5472.CAN-21-0684
Chronic Stress Effects on Tumor: Pathway and Mechanism.
Hong Hanqing,Ji Min,Lai Dongmei
Frontiers in oncology
Chronic stress is an emotional experience that occurs when people encounter something they cannot adapt to. Repeated chronic stress increases the risk of a variety of diseases, such as cardiovascular disease, depression, endocrine disease, inflammation and cancer. A growing body of research has shown that there is a link between chronic stress and tumor occurrence in both animal studies and clinical studies. Chronic stress activates the neuroendocrine system (hypothalamic-pituitary-adrenal axis) and sympathetic nervous system. Stress hormones promote the occurrence and development of tumors through various mechanisms. In addition, chronic stress also affects the immune function of the body, leading to the decline of immune monitoring ability and promote the occurrence of tumors. The mechanisms of chronic stress leading to tumor include inflammation, autophagy and epigenetics. These factors increase the proliferation and invasion capacity of tumor cells and alter the tumor microenvironment. Antagonists targeting adrenergic receptors have played a beneficial role in improving antitumor activity, as well as chemotherapy resistance and radiation resistance. Here, we review how these mechanisms contribute to tumor initiation and progression, and discuss whether these molecular mechanisms might be an ideal target to treat tumor.
10.3389/fonc.2021.738252