ArticleScience translational medicine2016
Dormant breast cancer micrometastases reside in specific bone marrow niches that regulate their transit to and from bone.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 1 of them a synthesis that pooled it.
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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
151 citing papers in PubMed, 1 synthesis or guideline pooled it, 234 citations in OpenAlex.
- The Role of Cytokines in the Metastasis of Solid Tumors to the Spine: Systematic Review.International journal of molecular sciences · 2023Pooled it
- Long-term outcome of (neo)adjuvant zoledronic acid therapy in locally advanced breast cancer.Breast cancer research and treatment · 2021Trial
- Metabolic consequences of perioperative oral carbohydrates in breast cancer patients - an explorative study.BMC cancer · 2019Trial
- Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives.Biomedicines · 2026Review
- Cytokine Regulation of the Bone Pre- and Metastatic Niches: Implications for Breast Cancer Dormancy.Cells · 2026Review
- From Bone Marrow Reserve to Metastatic Niche: How Neutrophil-Lineage Cells Shape Skeletal Colonization.International journal of molecular sciences · 2026Review
- Mechanisms of breast cancer dormancy in bone metastasis.Clinical & experimental metastasis · 2026Review
- Article
- Single-stranded DNA in the bone microenvironment promotes prostate cancer bone metastasis via the ITGA6-FAK pathway.Communications biology · 2026Article
- Review
- Hematopoietic Niche Hijacking in Bone Metastases: Roles of Megakaryocytes, Erythroid Lineage Cells, and Perivascular Stromal Subsets.Biomedicines · 2026Review
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Microenvironmental and Molecular Pathways Driving Dormancy Escape in Bone Metastases.International journal of molecular sciences · 2025Review
- Review
- Defining the Tumor-Bone axis: the role of extracellular vesicles in a crucial exchange route for breast cancer development and progression.Clinical & experimental metastasis · 2025Review
- Single-cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization.Cell genomics · 2025Article
- Metabolic landscape of disseminated cancer dormancy.Trends in cancer · 2025Review
- Breast cancer: pathogenesis and treatments.Signal transduction and targeted therapy · 2025Review
- The Breast to Bone (B2B) Cohort Study to Prevent, Detect and Improve Treatment of Metastatic Disease: Baseline Assessment, Description and Progress.International journal of environmental research and public health · 2025Article
91 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Breast cancer metastatic relapse can occur years after therapy, indicating that disseminated breast cancer cells (BCCs) have a prolonged dormant phase before becoming proliferative. A major site of disease dissemination and relapse is bone, although the critical signals that allow circulating BCCs to identify bone microvasculature, enter tissue, and tether to the microenvironment are poorly understood. Using real-time in vivo microscopy of bone marrow (BM) in a breast cancer xenograft model, we show that dormant and proliferating BCCs occupy distinct areas, with dormant BCCs predominantly found in E-selectin- and stromal cell-derived factor 1 (SDF-1)-rich perisinusoidal vascular regions. We use highly specific inhibitors of E-selectin and C-X-C chemokine receptor type 4 (CXCR4) (SDF-1 receptor) to demonstrate that E-selectin and SDF-1 orchestrate opposing roles in BCC trafficking. Whereas E-selectin interactions are critical for allowing BCC entry into the BM, the SDF-1/CXCR4 interaction anchors BCCs to the microenvironment, and its inhibition induces mobilization of dormant micrometastases into circulation. Homing studies with primary BCCs also demonstrate that E-selectin regulates their entry into bone through the sinusoidal niche, and immunohistochemical staining of patient BMs shows dormant micrometastatic disease adjacent to SDF-1(+) vasculature. These findings shed light on how BCCs traffic within the host, and suggest that simultaneous blockade of CXCR4 and E-selectin in patients could molecularly excise dormant micrometastases from the protective BM environment, preventing their emergence as relapsed disease.
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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.