The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
The perivascular niche regulates breast tumour dormancy
Open accessAbstract
In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumour cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumour biology. To address these questions, we used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumour-promoting factors derived from endothelial tip cells. Our work reveals that stable microvasculature constitutes a dormant niche, whereas sprouting neovasculature sparks micrometastatic outgrowth.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent studies are increasingly employing microvascular networks (µVNs)[21, 23, 24], where the permeability, architecture and diameters of vessels are more similar to those found in in vivo microvascular beds (Figure 2A) [21].”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [24]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Studies have shown that dormancy can be induced by endothelial derived factors[24], thus demonstrating the need for microfluidic models that recapitulate interactions between ECs and tumor cells, using for example µVNs.”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,338
The distribution of secondary growths in cancer of the breast.
Paget, S. (1889) · The Lancet · doi:10.1016/s0140-6736(00)49915-0 · Cited by 5,277
Dissemination and growth of cancer cells in metastatic sites
Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002) · Nature reviews. Cancer · doi:10.1038/nrc865 · Cited by 4,018
A perivascular origin for mesenchymal stem cells in multiple human organs
Crisan, M., Yap, S., Casteilla, L., Chen, C.-W., Corselli, M., Park, T. S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.003 · Cited by 3,991
Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET
Peinado, H., Alečković, M., Lavotshkin, S., Matei, I., Costa-Silva, B., Moreno-Bueno, G., Hergueta-Redondo, M., Williams, C., García-Santos, G., Ghajar, C. M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2753 · Cited by 3,715
Self-citationVEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche
Kaplan, R. N., Riba, R. D., Zacharoulis, S., Bramley, A. H., Vincent, L., Costa, C., MacDonald, D. D., Jin, D. K., Shido, K., Kerns, S. A., et al. (2005) · Nature · doi:10.1038/nature04186 · Cited by 3,288
Self-citationRequirement of Vascular Integrin α v β 3 for Angiogenesis
Brooks, P. C., Clark, R. A. F., & Cheresh, D. A. (1994) · Science · doi:10.1126/science.7512751 · Cited by 3,020
Angiogenesis: an organizing principle for drug discovery?
Folkman, J. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2115 · Cited by 2,299
A Perivascular Niche for Brain Tumor Stem Cells
Calabrese, C. R., Poppleton, H., Koçak, M., Hogg, T. L., Fuller, C. E., Hamner, J. B., Oh, E. Y., Gaber, M. W., Finklestein, D., Allen, M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.11.020 · Cited by 2,253
Endothelial and perivascular cells maintain haematopoietic stem cells
Ding, L., Saunders, T. L., Enikolopov, G., & Morrison, S. J. (2012) · Nature · doi:10.1038/nature10783 · Cited by 2,031
Flagged first, then by citations
Cited by
Sorted by citations
Microenvironmental regulation of tumor progression and metastasis
Quail, D. F., & Joyce, J. A. (2013) · Nature Medicine · doi:10.1038/nm.3394 · Cited by 7,994
Remodelling the extracellular matrix in development and disease
Bonnans, C., Chou, J., & Werb, Z. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3904 · Cited by 4,367
Emerging Biological Principles of Metastasis
Lambert, A. W., Pattabiraman, D. R., & Weinberg, R. A. (2017) · Cell · doi:10.1016/j.cell.2016.11.037 · Cited by 3,191
“For example, the apparent dormancy-inducing actions of the perivascular niche noted above seem to be reversed during neo-vascularization as sprouting endothelial tip cells secrete TGF-β1 and periostin (POSTN), which can break dormancy and promote tumor cell proliferation (Ghajar et al., 2013).”
Molecular principles of metastasis: a hallmark of cancer revisited
Fares, J., Fares, M. Y., Khachfe, H. H., Salhab, H. A., & Fares, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0134-x · Cited by 2,536
Concepts of extracellular matrix remodelling in tumour progression and metastasis
Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J., & Werb, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-18794-x · Cited by 2,296
Metadata
- Authors
- Ghajar, C. M., Peinado, H., Mori, H., Matei, I. R., Evason, K. J., Brazier, H., Almeida, D., Koller, A., Hajjar, K. A., Stainier, D. Y. R., Chen, E. I., Lyden, D., & Bissell, M. J.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Weill Cornell Medicine (US)
- University of California, San Francisco (US)
- Stony Brook University (US)
- Champalimaud Foundation (PT)
- Corresponding author
- Ghajar, Cyrus M.
- Bissell, Mina J.
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2013-06-02
- Volume
- 15
- Issue
- 7
- Pages
- 807-817
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC3826912
- OpenAlex
- W2155542819
- Cited by
- 1,148
- References
- 65
- Citations by year
- 2026: 62 · 2025: 68 · 2024: 70 · 2023: 86 · 2022: 89 · 2021: 122 · 2020: 125 · 2019: 97 · 2018: 98 · 2017: 69 · 2016: 89 · 2015: 64 · 2014: 78 · 2013: 29
- FWCI
- 46.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL042493, R01HL054737, R01HL090895, HL54737)
- National Cancer Institute (U54CA126552, U54CA143836, U01CA169538, R37CA064786)
- National Center for Research Resources (1 S10 RR023680-1, S10RR023680)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- breast cancer, tumor dormancy, disseminated tumor cells, perivascular niche, endothelial cells, thrombospondin-1, TGF-β1, periostin, organotypic culture, micrometastases, microcirculation
- MeSH terms
- Animals, Brain Neoplasms, Breast Neoplasms, Endothelium, Vascular, Female, Fluorescent Antibody Technique, Humans, Lung Neoplasms, Neovascularization, Pathologic, Tumor Cells, Cultured, Zebrafish, Cell Adhesion Molecules, Transforming Growth Factor beta, Neoplasm, Residual, Bone Marrow Neoplasms, Thrombospondin 1, Pericytes, Mice, Stem Cell Niche, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
