ArticleNeuro-oncology2013
Premetastatic soil and prevention of breast cancer brain metastasis.
Article in Neuro-oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 101 citations in OpenAlex.
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Serum S100A8/S100A9 is associated with increased risk of brain metastasis in patients with inflammatory breast cancer.medRxiv : the preprint server for health sciences · 2026Article
- MDSCs in Breast Cancer: Metastasis, Lipid Metabolism, and Therapeutics.Molecular cancer research : MCR · 2025Review
- Bioinformatic Characterization of Genes That Are Correlated to the Progression of Breast Cancer to Breast Cancer Brain Metastasis.Cancer reports (Hoboken, N.J.) · 2025Article
- The immune landscape in brain metastasis.Neuro-oncology · 2025Review
- Targeting immune checkpoints on myeloid cells: current status and future directions.Cancer immunology, immunotherapy : CII · 2025Review
- The diverse roles of neutrophils from protection to pathogenesis.Nature immunology · 2024Review
- Crosstalk between breast cancer-derived microRNAs and brain microenvironmental cells in breast cancer brain metastasis.Frontiers in oncology · 2024Review
- S100A8/A9 as a risk factor for breast cancer negatively regulated by DACH1.Biomarker research · 2023Article
- Mechanisms of Organ-Specific Metastasis of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- Identifying New Contributors to Brain Metastasis in Lung Adenocarcinoma: A Transcriptomic Meta-Analysis.Cancers · 2023Article
- Expression of S100A9 in adamantinomatous craniopharyngioma and its association with wet keratin formation.Experimental and therapeutic medicine · 2023Article
- Immune determinants of the pre-metastatic niche.Cancer cell · 2023Review
- Review
- Immune related biomarkers for cancer metastasis to the brain.Experimental hematology & oncology · 2022Review
- Metabolism in the progression and metastasis of brain tumors.Cancer letters · 2022Review
- Review
- Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis.Oncogene · 2022Article
- AMIGO2 contained in cancer cell-derived extracellular vesicles enhances the adhesion of liver endothelial cells to cancer cells.Scientific reports · 2022Article
- Harnessing nanomedicine for enhanced immunotherapy for breast cancer brain metastases.Drug delivery and translational research · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAs therapies for systemic cancer improve and patients survive longer, the risk for brain metastases increases. We evaluated whether immune mechanisms are involved in the development of brain metastasis.
methodsWe conducted our studies using BALB/c mice bearing syngeneic 4T1 mammary adenocarcinoma cells in the mammary gland.
resultsThe brains of mice bearing 4T1 tumors at day 14 had no detectable metastatic tumor cells but presented with marked accumulation of bone marrow-derived CD11b(+)Gr1(+) myeloid cells, which express high levels of inflammatory chemokines S100A8 and S100A9. In vitro, S100A9 attracts 4T1 cells through Toll-like receptor 4 and CD11b(+)Gr1(+) myeloid cells through Toll-like receptor 4 and the receptor for advanced glycation end-products. Systemic treatment of 4T1-bearing mice with anti-Gr1 (RB6-8C5) monoclonal antibody reduces accumulation of CD11b(+)Gr1(+) myeloid cells in the day-14 premetastatic brain as well as subsequent brain metastasis of 4T1 cells detected on day 30. Furthermore, treatment of 4T1 tumor-bearing mice with the cyclooxygenase-2 inhibitor celecoxib or genetic disruption of cyclooxygenase-2 in 4T1 cells inhibits the inflammatory chemokines and infiltration of CD11b(+)Gr1(+) myeloid cells in the premetastatic brain and subsequent formation of brain metastasis.
conclusionsOur results suggest that the primary tumor induces accumulation of CD11b(+)Gr1(+) myeloid cells in the brain to form "premetastatic soil" and inflammation mediators, such as S100A9, that attract additional myeloid cells as well as metastatic tumor cells. Celecoxib and anti-Gr1 treatment may be useful for blockade of these processes, thereby preventing brain metastasis in patients with breast cancer.
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