Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_CE5A6DC34AFB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation.
Journal
Cancers
Author(s)
Saltarin F., Wegmüller A., Bejarano L., Ildiz E.S., Zwicky P., Vianin A., Spadin F., Soukup K., Wischnewski V., Engelhardt B., Deutsch U., J Marques I., Frenz M., Joyce J.A., Lyck R.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
20/10/2023
Peer-reviewed
Oui
Volume
15
Number
20
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Melanoma frequently metastasises to the brain, and a detailed understanding of the molecular and cellular mechanisms underlying melanoma cell extravasation across the blood-brain barrier (BBB) is important for preventing brain metastasis formation. Making use of primary mouse brain microvascular endothelial cells (pMBMECs) as an in vitro BBB model, we imaged the interaction of melanoma cells into pMBMEC monolayers. We observed exclusive junctional intercalation of melanoma cells and confirmed that melanoma-induced pMBMEC barrier disruption can be rescued by protease inhibition. Interleukin (IL)-1β stimulated pMBMECs or PECAM-1-knockout (-ko) pMBMECs were employed to model compromised BBB barrier properties in vitro and to determine increased melanoma cell intercalation compared to pMBMECs with intact junctions. The newly generated brain-homing melanoma cell line YUMM1.1-BrM4 was used to reveal increased in vivo extravasation of melanoma cells across the BBB of barrier-compromised PECAM-1-deficient mice compared to controls. Taken together, our data indicate that preserving BBB integrity is an important measure to limit the formation of melanoma-brain metastasis.
Keywords
blood-brain barrier (BBB), cell extravasation, endothelial junctions, melanoma, metastasis
Pubmed
Web of science
Open Access
Yes
Create date
06/11/2023 14:17
Last modification date
08/08/2024 7:40
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