ArticleJournal of experimental & clinical cancer research : CR2023
Chronic stress induces pulmonary epithelial cells to produce acetylcholine that remodels lung pre-metastatic niche of breast cancer by enhancing NETosis.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Chronic psychosocial stress: a role in breast cancer etiology?Frontiers in oncology · 2026Pooled it
- Neuro-immune interactions in tumors, immune-related disorders, and infections.Signal transduction and targeted therapy · 2026Review
- Associations Between Cancer-Related Self-Efficacy, Coping Styles, and Perceived Stress in Patients with Lung Cancer: A Cross-Sectional Mediation Analysis.Journal of clinical medicine · 2026Article
- Electroacupuncture enhances anti-tumor immunity in TNBC by reducing NE release and blocking α2-AR-mediated NGF/Hippo signaling.Chinese medicine · 2026Article
- Chronic stress drives gastric cancer lymph node metastasis via NETosis through a feedforward ACh-NGF axis-mediated PKC-γ/STAT3 pathway.Oncogene · 2026Article
- Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.Cell communication and signaling : CCS · 2026Review
- The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications.BMC medicine · 2026Review
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- Neutrophil extracellular traps in the tumor microenvironment, metastasis, therapy, and beyond: advances, challenges, and perspectives.Journal of hematology & oncology · 2026Review
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- Inhibition of VNN1-Induced ROS-Dependent NETs Formation Alleviates Lung Injury and Systemic Inflammation in Sepsis Mice.Journal of inflammation research · 2026Article
- Study on key markers of NETosis: predictive indicator for postoperative frailty following complete cytoreductive surgery in advanced ovarian cancer.Frontiers in immunology · 2026Article
- Neuroimmunological Mechanisms of Xiao-Yao-San Against Chronic Stress-Induced Colorectal Cancer: A Bioinformatics and Single-Cell Sequencing Study.Cancer management and research · 2026Article
- Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.Cancer communications (London, England) · 2026Review
- The role of NETosis in breast cancer: mechanistic insights and biomarker potential.Breast cancer research : BCR · 2025Review
- Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.Biomarker research · 2025Review
- The role of acetylcholine and its receptors in tumor immune regulation: mechanisms and potential therapeutic targets.Molecular cancer · 2025Review
- Progress in the mechanistic understanding of NETs formation in cancer.Medical oncology (Northwood, London, England) · 2025Review
- Chronic stress: a fourth etiology in tumorigenesis?Molecular cancer · 2025Review
- Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic stress promotes most hallmarks of cancer through impacting the malignant tissues, their microenvironment, immunity, lymphatic flow, etc. Existing studies mainly focused on the roles of stress-induced activation of systemic sympathetic nervous system and other stress-induced hormones, the organ specificity of chronic stress in shaping the pre-metastatic niche remains largely unknown. This study investigated the role of chronic stress in remodeling lung pre-metastatic niche of breast cancer.
methodsBreast cancer mouse models with chronic stress were constructed by restraint or unpredictable stress. Expressions of tyrosine hydroxylase, vesicular acetylcholine transporter (VAChT), EpCAM and NETosis were examined by immunofluorescence and confocal microscopy. mRNA and protein levels of choline acetyltransferase (ChAT), VAChT, and peptidylarginine deiminase 4 were detected by qRT-PCR and Western blotting, respectively. Immune cell subsets were analyzed by flow cytometry. Acetylcholine (ACh) and chemokines were detected by ELISA and multi chemokine array, respectively. ChAT in lung tissues from patients was examined by immunohistochemistry.
resultsBreast cancer-bearing mice suffered chronic stress metastasized earlier and showed more severe lung metastasis than did mice in control group. VAChT, ChAT and ChAT
conclusionsChronic stress promotes production of CXCL2 that recruits neutrophils into lung, and induces pulmonary epithelial cells to produce ACh that enhances NETosis of neutrophils. Our findings demonstrate for the first time that chronic stress induced epithelial cell derived ACh plays a key role in remodeling lung pre-metastatic niche of breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.