ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2019
VLA-4 mediated adhesion of melanoma cells on the blood-brain barrier is the critical cue for melanoma cell intercalation and barrier disruption.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 22 citations in OpenAlex.
- VLA-4 integrin modulates cellular responses to sorafenib in metastasis-related processes of B16F10 melanoma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
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- Brain neurovascular unit in response to intra- and extra-central nervous system cancers: implications, mechanisms, and challenges.Cancer cell international · 2025Review
- DNA Aptamer-Polymer Conjugates for Selective Targeting of Integrin α4β1ACS applied materials & interfaces · 2025Article
- Deciphering the Blood-Brain Barrier Paradox in Brain Metastasis Development and Therapy.Cancers · 2025Review
- Investigation of a fluorescent reporter microenvironment niche labeling strategy in experimental brain metastasis.iScience · 2024Article
- Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation.Cancers · 2023Article
- The origin of brain malignancies at the blood-brain barrier.Cellular and molecular life sciences : CMLS · 2023Review
- Tumour-derived extracellular vesicle based vaccines for melanoma treatment.Drug delivery and translational research · 2023Review
- Integrins and the Metastasis-like Dissemination of Acute Lymphoblastic Leukemia to the Central Nervous System.Cancers · 2023Review
- Review
- Glycosylation as a regulator of site-specific metastasis.Cancer metastasis reviews · 2022Review
- Genes that Mediate Metastasis across the Blood-Brain Barrier.Trends in cancer · 2020Review
- Combined VLA-4-Targeted Radionuclide Therapy and Immunotherapy in a Mouse Model of Melanoma.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2018Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanoma is the most aggressive skin cancer in humans. One severe complication is the formation of brain metastasis, which requires extravasation of melanoma cells across the tight blood-brain barrier (BBB). Previously, VLA-4 has been assigned a role for the adhesive interaction of melanoma cells with non-BBB endothelial cells. However, the role of melanoma VLA-4 for breaching the BBB remained unknown. In this study, we used a mouse in vitro BBB model and imaged the shear resistant arrest of melanoma cells on the BBB. Similar to effector T cells, inflammatory conditions of the BBB increased the arrest of melanoma cells followed by a unique post-arrest behavior lacking immediate crawling. However, over time, melanoma cells intercalated into the BBB and compromised its barrier properties. Most importantly, antibody ablation of VLA-4 abrogated melanoma shear resistant arrest on and intercalation into the BBB and protected the BBB from barrier breakdown. A tissue microarray established from human brain metastasis revealed that indeed a majority of 92% of all human melanoma brain metastases stained VLA-4 positive. We propose VLA-4 as a target for the inhibition of brain metastasis formation in the context of personalized medicine identifying metastasizing VLA-4 positive melanoma.
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