ArticleThe Journal of experimental medicine2020
Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.
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The trial behind it
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
64 citing papers in PubMed, 95 citations in OpenAlex.
- A CT-based radiomics model to predict subsequent brain metastasis in patients with ALK-rearranged non-small cell lung cancer undergoing crizotinib treatment.Thoracic cancer · 2022Trial
- Hypoxia or tobacco-smoke exposure induce region-specific microvascular remodeling in the brain.Scientific reports · 2026Article
- The immune microenvironment of the central nervous system and neuromodulation: new perspectives in lung cancer brain metastases research.Frontiers in immunology · 2026Review
- Parthenolide and Its Derivatives in the Treatment of Respiratory Tract Diseases: Therapeutic Effects and Molecular Mechanisms.Drug design, development and therapy · 2026Review
- Case Report: Management of cervical intramedullary spinal cord metastasis from NSCLC with a literature review.Frontiers in surgery · 2026Article
- Brain metastases from non-small cell lung cancer: molecular subtypes and emerging CNS-directed precision therapies.Frontiers in oncology · 2026Review
- Single-Cell Transcriptomics Reveals the Potential Role of GZMK+ CD8+ T Cells in Cell Senescence of Triple-Negative Breast Cancer.International journal of genomics · 2026Article
- Lung cancer cells upregulate stearoyl-CoA desaturase 1 in microglia by activating the STAT3 pathway to change microglial inflammatory response in lung-to-brain metastases.Cell death & disease · 2025Article
- Aβ Deposition in Extracellular Space Disrupts Glial-Neuron Communication and Triggers Alzheimer's Disease.Aging and disease · 2025Review
- Ghrelin-induced neuronal NPY promotes brain metastasis in lung cancer patients with low BMI.Nature communications · 2025Article
- Integrating multi-omics to unveil PSMD12 as a critical gene in promoting brain metastases of lung adenocarcinoma.Journal of translational medicine · 2025Article
- Retraction Note: Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions.Breast cancer research : BCR · 2025Article
- HIV-1 gp120 Interactions with Nicotine Modulate Mitochondrial Network Properties and Amyloid Release in Microglia.Neurochemical research · 2025Article
- Cell Senescence-Related Genes as Biomarkers for Prognosis and Immunotherapeutic Response in Colon Cancer.Biochemical genetics · 2025Article
- Long non-coding RNA Malat1 modulates CXCR4 expression to regulate the interaction between induced neural stem cells and microglia following closed head injury.Stem cell research & therapy · 2025Article
- Deciphering the Blood-Brain Barrier Paradox in Brain Metastasis Development and Therapy.Cancers · 2025Review
- Bioactive compounds in Chinese herbal medicine: anti-inflammatory mechanisms targeting neurological disorders.Frontiers in nutrition · 2025Review
- Secukinumab is not associated with cancer recurrence or progression in patients with spondyloarthritis and history of neoplastic disease.Rheumatology international · 2024Article
- Pan-cell death-related signature reveals tumor immune microenvironment and optimizes personalized therapy alternations in lung adenocarcinoma.Scientific reports · 2024Article
- Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity.Cell reports. Medicine · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Up to 40% of lung cancer patients develop brain metastasis, and the median survival of these patients remains less than 6 months. Smoking is associated with lung cancer. However, how smoking impacts the development of brain metastasis remains elusive. We examined 281 lung cancer patients with distant metastasis and found that smokers exhibited a significantly high incidence of brain metastasis. We found that nicotine enhanced brain metastasis, while a depletion of microglia suppressed this effect in vivo. Nicotine skewed the polarity of microglia to the M2 phenotype, thereby increasing the secretion of IGF-1 and CCL20, which promoted tumor progression and stemness. Importantly, nicotine enhanced the expression of SIRPα in microglia and restricted their phagocytic ability. We also identified a compound, parthenolide, that suppressed brain metastasis by blocking M2 polarization. Our results indicate that nicotine promotes brain metastasis by skewing the polarity of M2 microglia, which enhances metastatic tumor growth. Our results also highlight a potential risk of using nicotine for tobacco cessation.
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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 OpenQuestion graph.