ArticlePloS one2009
The vascular basement membrane as "soil" in brain metastasis.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 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.
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Who cites it
184 citing papers in PubMed, 1 synthesis or guideline pooled it, 331 citations in OpenAlex.
- International consensus guidelines for scoring the histopathological growth patterns of liver metastasis.British journal of cancer · 2017Guideline
- Brain metastasis: Opportunities for novel therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Review
- Is cancer the result of uncontrolled cellular growth? a glance into the tumorigenic process.Cancer cell international · 2026Review
- Suppressive effects on metastasis and tumor growth by the knockout of chemokine receptors in a canine cutaneous lymphoma model.The Journal of veterinary medical science · 2026Article
- Breast cancer brain metastasis: from molecular insights to therapeutic innovation.Frontiers in immunology · 2026Review
- Epigenomic and Metabolic Interplay in the Development of Metastatic Brain Tumors.Oncology research · 2026Review
- A large scale multi-dataset investigation of brain metastases distribution based on primary cancer type.BMC cancer · 2025Article
- Immune Checkpoint Inhibition in Patients with Brain Metastases from Non-Small-Cell Lung Cancer: Emerging Mechanisms and Personalized Clinical Strategies.International journal of molecular sciences · 2025Review
- Brain Metastasis: A Literary Review of the Possible Relationship Between Hypoxia and Angiogenesis in the Growth of Metastatic Brain Tumors.International journal of molecular sciences · 2025Review
- Role and Mechanisms of Angiogenesis in Tumours.Biology · 2025Review
- Molecular Underpinnings of Brain Metastases.International journal of molecular sciences · 2025Review
- The role and regulation of integrins in cell migration and invasion.Nature reviews. Molecular cell biology · 2025Review
- Progress in personalized immunotherapy for patients with brain metastasis.NPJ precision oncology · 2025Review
- Deciphering the Blood-Brain Barrier Paradox in Brain Metastasis Development and Therapy.Cancers · 2025Review
- Differential stiffness between brain vasculature and parenchyma promotes metastatic infiltration through vessel co-option.Nature cell biology · 2024Article
- Distinct tumor architectures and microenvironments for the initiation of breast cancer metastasis in the brain.Cancer cell · 2024Article
- Proteomic insights into breast cancer response to brain cell-secreted factors.Scientific reports · 2024Article
- The murine metastatic microenvironment of experimental brain metastases of breast cancer differs by host age in vivo: a proteomic study.Clinical & experimental metastasis · 2024Article
- Stress in the metastatic journey - the role of cell communication and clustering in breast cancer progression and treatment resistance.Disease models & mechanisms · 2024Article
124 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Brain-specific homing and direct interactions with the neural substance are prominent hypotheses for brain metastasis formation and a modern manifestation of Paget's "seed and soil" concept. However, there is little direct evidence for this "neurotropic" growth in vivo. In contrast, many experimental studies have anecdotally noted the propensity of metastatic cells to grow along the exterior of pre-existing vessels of the CNS, a process termed vascular cooption. These observations suggest the "soil" for malignant cells in the CNS may well be vascular, rather than neuronal. We used in vivo experimental models of brain metastasis and analysis of human clinical specimens to test this hypothesis. Indeed, over 95% of early micrometastases examined demonstrated vascular cooption with little evidence for isolated neurotropic growth. This vessel interaction was adhesive in nature implicating the vascular basement membrane (VBM) as the active substrate for tumor cell growth in the brain. Accordingly, VBM promoted adhesion and invasion of malignant cells and was sufficient for tumor growth prior to any evidence of angiogenesis. Blockade or loss of the beta1 integrin subunit in tumor cells prevented adhesion to VBM and attenuated metastasis establishment and growth in vivo. Our data establishes a new understanding of CNS metastasis formation and identifies the neurovasculature as the critical partner for such growth. Further, we have elucidated the mechanism of vascular cooption for the first time. These findings may help inform the design of effective molecular therapies for patients with fatal CNS malignancies.
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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.