ArticleThe American journal of pathology2013
Pazopanib inhibits the activation of PDGFRβ-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
- Astrocyte heterogeneity in brain metastases.Molecular oncology · 2026Review
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Transcriptomic Profiling of Paired Primary Tumors and CNS Metastases in Breast Cancer Reveals Immune Modulation Signatures.International journal of molecular sciences · 2025Article
- Astrocyte involvement in brain metastasis: from biological mechanisms to therapeutic strategies.Cancer metastasis reviews · 2025Review
- TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells.Cancer discovery · 2025Article
- Analysis of neuroglia and immune cells in the tumor microenvironment of breast cancer brain metastasis.Cancer biology & therapy · 2024Review
- Determining M2 macrophages content for the anti-tumor effects of metal-organic framework-encapsulated pazopanib nanoparticles in breast cancer.Journal of nanobiotechnology · 2024Article
- CaInternational journal of molecular sciences · 2023Article
- TME-targeted approaches of brain metastases and its clinical therapeutic evidence.Frontiers in immunology · 2023Review
- Tumor Immune Microenvironment of Brain Metastases: Toward Unlocking Antitumor Immunity.Cancer discovery · 2022Review
- A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.EMBO molecular medicine · 2022Article
- Glioblastoma Microenvironment and Cellular Interactions.Cancers · 2022Review
- Glial and myeloid heterogeneity in the brain tumour microenvironment.Nature reviews. Cancer · 2021Review
- Salting the Soil: Targeting the Microenvironment of Brain Metastases.Molecular cancer therapeutics · 2021Review
- Stromal Platelet-Derived Growth Factor Receptor-β Signaling Promotes Breast Cancer Metastasis in the Brain.Cancer research · 2021Article
- Sorafenib Modulates the LPS- and Aβ-Induced Neuroinflammatory Response in Cells, Wild-Type Mice, and 5xFAD Mice.Frontiers in immunology · 2021Article
- Old Stars and New Players in the Brain Tumor Microenvironment.Frontiers in cellular neuroscience · 2021Review
- Article
- Proteomic Analysis of the Breast Cancer Brain Metastasis Microenvironment.International journal of molecular sciences · 2019Article
- Innovative Therapeutic Strategies for Effective Treatment of Brain Metastases.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Brain metastases occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. Brain colonization of cancer cells occurs in a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although a neuroinflammatory response has been documented in brain metastasis, its contribution to cancer progression and therapy remains poorly understood. Using an experimental brain metastasis model, we characterized the brain metastatic microenvironment of brain tropic, HER2-transfected MDA-MB-231 human breast carcinoma cells (231-BR-HER2). A previously unidentified subpopulation of metastasis-associated astrocytes expressing phosphorylated platelet-derived growth factor receptor β (at tyrosine 751; p751-PDGFRβ) was identified around perivascular brain micrometastases. p751-PDGFRβ(+) astrocytes were also identified in human brain metastases from eight craniotomy specimens and in primary cultures of astrocyte-enriched glial cells. Previously, we reported that pazopanib, a multispecific tyrosine kinase inhibitor, prevented the outgrowth of 231-BR-HER2 large brain metastases by 73%. Here, we evaluated the effect of pazopanib on the brain neuroinflammatory microenvironment. Pazopanib treatment resulted in 70% (P = 0.023) decrease of the p751-PDGFRβ(+) astrocyte population, at the lowest dose of 30 mg/kg, twice daily. Collectively, the data identify a subpopulation of activated astrocytes in the subclinical perivascular stage of brain metastases and show that they are inhibitable by pazopanib, suggesting its potential to prevent the development of brain micrometastases in breast cancer patients.
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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.