ArticleCancers2022
CXCR2 Mediates Distinct Neutrophil Behavior in Brain Metastatic Breast Tumor.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
24 citing papers in PubMed, 35 citations in OpenAlex.
- Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Soluble E-cadherin-CXCL1-CXCR2 axis as a therapeutic vulnerability in inflammatory breast cancer brain metastasis.Neuro-oncology · 2026Article
- Quantifying the Dual Effect of Antitumor and Pro-Tumor Human Neutrophils on Natural Killer Cell Behaviors in a Microphysiological System.ACS biomaterials science & engineering · 2026Article
- Hijacking emergency granulopoiesis: Neutrophil ontogeny and reprogramming in cancer.Molecular oncology · 2026Review
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Direct Targeting of CXCR2 Receptor Inhibits Neuroblastoma Growth: An In Vitro Assessment.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025Review
- Therapeutic potential of tumor-associated neutrophils: dual role and phenotypic plasticity.Signal transduction and targeted therapy · 2025Review
- Mitochondrial reactive oxygen species promote cancer metastasis and tumor microenvironment immunosuppression through gasdermin D.Cell death discovery · 2025Article
- Selective anti-CXCR2 receptor blockade by AZD5069 inhibits CXCL8-mediated pro-tumorigenic activity in human thyroid cancer cells in vitro.Journal of endocrinological investigation · 2025Article
- NETs - as predictors and targets of supportive therapy for cancer treatment.Frontiers in immunology · 2025Review
- Neutrophils in the premetastatic niche: key functions and therapeutic directions.Molecular cancer · 2024Review
- Magnetically Integrated Tumor-Vascular Interface System to Mimic Pro-angiogenic Endothelial Dysregulations for On-Chip Drug Testing.ACS applied materials & interfaces · 2024Article
- A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy.Scientific reports · 2024Article
- Neutrophil Extracellular Traps in Breast Cancer: Roles in Metastasis and Beyond.Journal of Cancer · 2024Review
- Neutrophils in triple-negative breast cancer: an underestimated player with increasingly recognized importance.Breast cancer research : BCR · 2023Review
- Neutrophil extracellular traps primed intercellular communication in cancer progression as a promising therapeutic target.Biomarker research · 2023Review
- Diverse Neutrophil Functions in Cancer and Promising Neutrophil-Based Cancer Therapies.International journal of molecular sciences · 2022Review
- Cytokine Landscape in Central Nervous System Metastases.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Brain metastasis is one of the main causes of mortality among breast cancer patients, but the origins and the mechanisms that drive this process remain poorly understood. Here, we report that the upregulation of certain CXCR2-associated ligands in the brain metastatic variants of the breast cancer cells (BrM) dynamically activate the corresponding CXCR2 receptors on the neutrophils, thereby resulting in the modulation of certain key functional neutrophil responses towards the BrM. Using established neutrophil-tumor biomimetic co-culture models, we show that the upregulation of CXCR2 increases the recruitment of Tumor-Associated Neutrophils (TANs) towards the BrM, to enable location-favored formation of Neutrophil Extracellular Traps (NETs). Inhibition of CXCR2 using small molecule antagonist AZD5069 reversed this behavior, limiting the neutrophil responses to the BrM and retarding the reciprocal tumor development. We further demonstrate that abrogation of NETs formation using Neutrophil Elastase Inhibitor (NEI) significantly decreases the influx of neutrophils towards BrM but not to their parental tumor, suggesting that CXCR2 activation could be used by the brain metastatic tumors as a mechanism to program the tumor-infiltrating TANs into a pro-NETotic state, so as to assume a unique spatial distribution that assists in the subsequent migration and invasion of the metastatic tumor cells. This new perspective indicates that CXCR2 is a critical target for suppressing neutrophilic inflammation in brain metastasis.
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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.