ArticleScience advances2021
The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 62 citations in OpenAlex.
- Review
- Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial.Nature medicine · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Olink Proteomics Reveals CCL2 Aggravates Perihematomal Edema After Intracerebral Hemorrhage in High-Altitude Migrants Via CCR2/NF-κB-Mediated Blood-Brain Barrier Disruption.CNS neuroscience & therapeutics · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Breast cancer brain metastasis: from molecular insights to therapeutic innovation.Frontiers in immunology · 2026Review
- Mechanobiology of the blood-brain barrier during development, disease and ageing.Nature communications · 2025Review
- Modeling metastasis - leveraging novel tools to streamline discovery in advanced cancer.Disease models & mechanisms · 2025Review
- Microfluidic Systems to Mimic the Blood-Brain Barrier: from Market to Engineering Challenges and Perspectives.ACS biomaterials science & engineering · 2025Review
- Molecular Underpinnings of Brain Metastases.International journal of molecular sciences · 2025Review
- Deciphering the Blood-Brain Barrier Paradox in Brain Metastasis Development and Therapy.Cancers · 2025Review
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- Choroid plexus CCL2‒CCR2 signaling orchestrates macrophage recruitment and cerebrospinal fluid hypersecretion in hydrocephalus.Acta pharmaceutica Sinica. B · 2024Article
- Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages.Cancer gene therapy · 2024Article
- Dissecting the MUC5AC/ANXA2 signaling axis: implications for brain metastasis in lung adenocarcinoma.Experimental & molecular medicine · 2024Article
- Hydrophobic surface induced pro-metastatic cancer cells forBioactive materials · 2024Article
- Extracellular vesicles set the stage for brain plasticity and recovery by multimodal signalling.Brain : a journal of neurology · 2024Review
- The Role of Microglia in Brain Metastases: Mechanisms and Strategies.Aging and disease · 2024Review
- Micro/nanosystems for controllable drug delivery to the brain.Innovation (Cambridge (Mass.)) · 2024Review
- Advancements in strategies for overcoming the blood-brain barrier to deliver brain-targeted drugs.Frontiers in aging neuroscience · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Although brain metastases are common in cancer patients, little is known about the mechanisms of cancer extravasation across the blood-brain barrier (BBB), a key step in the metastatic cascade that regulates the entry of cancer cells into the brain parenchyma. Here, we show, in a three-dimensional in vitro BBB microvascular model, that astrocytes promote cancer cell transmigration via their secretion of C-C motif chemokine ligand 2 (CCL2). We found that this chemokine, produced primarily by astrocytes, promoted the chemotaxis and chemokinesis of cancer cells via their C-C chemokine receptor type 2 (CCR2), with no notable changes in vascular permeability. These findings were validated in vivo, where CCR2-deficient cancer cells exhibited significantly reduced rates of arrest and transmigration in mouse brain capillaries. Our results reveal that the CCL2-CCR2 astrocyte-cancer cell axis plays a fundamental role in extravasation and, consequently, metastasis to the brain.
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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.