ArticleCancer research2023
Active Remodeling of Capillary Endothelium via Cancer Cell-Derived MMP9 Promotes Metastatic Brain Colonization.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- The Origin of Cancer-Associated Fibroblasts (CAFs) in Brain Metastases: Seven Hypotheses and Current Evidence.Cancers · 2026Review
- An MRI Atlas of Regional Brain Vulnerability to Metastatic Disease.medRxiv : the preprint server for health sciences · 2026Article
- Multiscale systems modelling of communication networks in brain metastasis.Experimental & molecular medicine · 2026Review
- Single-cell profiling reveals peripheral blood immune landscape remodelling in breast cancer lymph node metastasis.Clinical and translational medicine · 2026Article
- Nuclear Mechanotransduction Across the Metastatic Cascade: Decoding Spatiotemporal Heterogeneity in Cancer Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Preventive strategies against brain metastases: current state of the art and future directions.Neurological research and practice · 2026Review
- Cell viscosity influences haematogenous dissemination and metastatic extravasation of tumour cells.Nature materials · 2026Article
- Fast label-free live imaging with FlowVision reveals key principles of cancer cell arrest on endothelial monolayers.The EMBO journal · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Dynamic junction remodeling and transient vascular disruption during cancer cell extravasation across the blood-brain barrier.Frontiers in cell and developmental biology · 2026Article
- Voxel-accurate MRI-microscopy Correlation Enables AI-powered Prediction of Brain Disease States.Theranostics · 2026Article
- Epigenetic drivers of metalloproteinases and metastasis.Trends in cell biology · 2025Review
- Review
- A workflow for semi-automated volume correlative light microscopy and transmission electron tomography.Journal of microscopy · 2025Article
- Clinical Features, Molecular Biology, and the Metastatic Microenvironment in Lung Cancer Brain Metastases: Implications for Treatment Decisions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Metastasis-promoting functions of myeloid cells.Cancer metastasis reviews · 2025Review
- Article
- A Comprehensive Analysis of the Clinical Significance and Underlying Oncogenic Roles of Specific MMPs in Gastric Carcinoma Reveals their Potential Roles in Prognosis and Therapy.Current molecular medicine · 2025Article
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Authors and funding
25 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crossing the blood-brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding of the mechanisms of cancer cell extravasation from brain microcapillaries is limited as the underlying cellular and molecular processes cannot be adequately investigated using in vitro models and endpoint in vivo experiments. Using ultrastructural and functional imaging, we demonstrate that dynamic changes of activated brain microcapillaries promote the mandatory first steps of brain colonization. Successful extravasation of arrested cancer cells occurred when adjacent capillary endothelial cells (EC) entered into a distinct remodeling process. After extravasation, capillary loops were formed, which was characteristic of aggressive metastatic growth. Upon cancer cell arrest in brain microcapillaries, matrix-metalloprotease 9 (MMP9) was expressed. Inhibition of MMP2/9 and genetic perturbation of MMP9 in cancer cells, but not the host, reduced EC projections, extravasation, and brain metastasis outgrowth. These findings establish an active role of ECs in the process of cancer cell extravasation, facilitated by cross-talk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it. SIGNIFICANCE: Tracking single extravasating cancer cells using multimodal correlative microscopy uncovers a brain seeding mechanism involving endothelial remodeling driven by cancer cell-derived MMP9, which might enable the development of approaches to prevent brain metastasis. See related commentary by McCarty, p. 1167.
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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.