ArticleScientific reports2018
Metastatic Brain Tumors Disrupt the Blood-Brain Barrier and Alter Lipid Metabolism by Inhibiting Expression of the Endothelial Cell Fatty Acid Transporter Mfsd2a.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
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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
90 citing papers in PubMed, 150 citations in OpenAlex.
- MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.Molecular biomedicine · 2026Review
- The regulatory network of Mfsd2a in cerebral ischemia: a novel time-targeted intervention framework.Molecular biology reports · 2026Review
- Single-cell and spatial transcriptomes reveal oligodendrocyte remodeling fatty acid metabolism microenvironment of lung cancer brain metastases.Journal of translational medicine · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Multi-omics single-cell dissection of malignant epithelial heterogeneity identifies GJB2 as an EMT-driving biomarker in triple-negative breast cancer.BMC medical genomics · 2026Article
- Trastuzumab deruxtecan efficacy, FcRn-facilitated penetration of the blood-tumor barrier, and distribution to tumor cells in HER2+ brain metastasis model systems.Neuro-oncology · 2026Article
- Consequences of irradiation on blood-brain tumor barrier model of Diffuse Midline Glioma: characterization of physical and metabolic properties.Fluids and barriers of the CNS · 2026Article
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Bidirectional roles of meningeal lymphatic vessels in brain metastases: friend and foe.Frontiers in oncology · 2026Review
- MFSD2A: a molecular nexus linking blood-brain barrier, lipid metabolism, and ischemia-reperfusion injury.Cellular & molecular biology letters · 2025Review
- High Levels of Endogenous Omega-3 Fatty Acids Promote Dendritic Cell Antigen Presentation and Improve Dendritic Cell-Based Cancer Vaccine Efficacy in Mice.Cancer immunology research · 2025Article
- A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers.Nature communications · 2025Article
- Review
- Near-Infrared Photoimmunotherapy in Brain Tumors-An Unexplored Frontier.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Molecular Underpinnings of Brain Metastases.International journal of molecular sciences · 2025Review
- Cancer brain metastasis: molecular mechanisms and therapeutic strategies.Molecular biomedicine · 2025Review
- Mfsd2a suppresses colorectal cancer progression and liver metastasis via the S100A14/STAT3 axis.Journal of translational medicine · 2025Article
- Targeting Glucose Transporter 1 (GLUT1) in Cancer: Molecular Mechanisms and Nanomedicine Applications.International journal of nanomedicine · 2025Review
- Combination immunotherapy and anti-angiogenic therapy shows promising efficacy in NSCLC patients with recurrent or refractory brain metastases and negative driver genes.Frontiers in immunology · 2025Observational
- MicroRNAs in Lung Cancer Brain Metastasis.International journal of molecular sciences · 2024Review
30 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
6 authors at 1 institution in 1 country.
Funding
Abstract
Disruption of the blood-brain barrier (BBB) by cancer cells is linked to metastatic tumor initiation and progression; however, the pathways that drive these events remain poorly understood. Here, we have developed novel patient-derived xenograft (PDX) models of brain metastases that recapitulate pathological growth features found in original patient samples, thus allowing for analysis of BBB disruption by tumor cells. We report that the BBB is selectively disrupted in brain metastases, in part, via inhibition of the endothelial cell-expressed docosahexaenoic acid (DHA) transporter, major facilitator superfamily domain 2a (Mfsd2a). Loss of Mfsd2a expression in the tumor endothelium results in enhanced BBB leakage, but reduced DHA transport and altered lipid metabolism within metastases. Mfsd2a expression in normal cerebral endothelial cells is cooperatively regulated by TGFβ and bFGF signaling pathways, and these pathways are pathologically diminished in the brain metastasis endothelium. These results not only reveal a fundamental pathway underlying BBB disruption by metastatic cancer cells, but also suggest that restoring DHA metabolism in the brain tumor microenvironment may be a novel therapeutic strategy to block metastatic cell growth and survival.
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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 Socratic graph.