Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation
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 end...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/20/5071 |
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| author | Federico Saltarin Adrian Wegmüller Leire Bejarano Ece Su Ildiz Pascale Zwicky Andréj Vianin Florentin Spadin Klara Soukup Vladimir Wischnewski Britta Engelhardt Urban Deutsch Ines J. Marques Martin Frenz Johanna A. Joyce Ruth Lyck |
| author_facet | Federico Saltarin Adrian Wegmüller Leire Bejarano Ece Su Ildiz Pascale Zwicky Andréj Vianin Florentin Spadin Klara Soukup Vladimir Wischnewski Britta Engelhardt Urban Deutsch Ines J. Marques Martin Frenz Johanna A. Joyce Ruth Lyck |
| author_sort | Federico Saltarin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T21:21:35Z |
| format | Article |
| id | doaj.art-60ece8c9de224357a3e954b9b6b0090f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:21:35Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-60ece8c9de224357a3e954b9b6b0090f2023-11-19T16:00:09ZengMDPI AGCancers2072-66942023-10-011520507110.3390/cancers15205071Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and ExtravasationFederico Saltarin0Adrian Wegmüller1Leire Bejarano2Ece Su Ildiz3Pascale Zwicky4Andréj Vianin5Florentin Spadin6Klara Soukup7Vladimir Wischnewski8Britta Engelhardt9Urban Deutsch10Ines J. Marques11Martin Frenz12Johanna A. Joyce13Ruth Lyck14Theodor Kocher Institute, University of Bern, 3012 Bern, SwitzerlandTheodor Kocher Institute, University of Bern, 3012 Bern, SwitzerlandDepartment of Oncology, University of Lausanne, 1011 Lausanne, SwitzerlandTheodor Kocher Institute, University of Bern, 3012 Bern, SwitzerlandTheodor Kocher Institute, University of Bern, 3012 Bern, SwitzerlandDepartment of Developmental Biology and Regeneration, Institute of Anatomy, University of Bern, 3012 Bern, SwitzerlandInstitute of Applied Physics, University of Bern, 3012 Bern, SwitzerlandDepartment of Oncology, University of Lausanne, 1011 Lausanne, SwitzerlandDepartment of Oncology, University of Lausanne, 1011 Lausanne, SwitzerlandTheodor Kocher Institute, University of Bern, 3012 Bern, SwitzerlandTheodor Kocher Institute, University of Bern, 3012 Bern, SwitzerlandDepartment of Developmental Biology and Regeneration, Institute of Anatomy, University of Bern, 3012 Bern, SwitzerlandInstitute of Applied Physics, University of Bern, 3012 Bern, SwitzerlandDepartment of Oncology, University of Lausanne, 1011 Lausanne, SwitzerlandTheodor Kocher Institute, University of Bern, 3012 Bern, SwitzerlandMelanoma 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.https://www.mdpi.com/2072-6694/15/20/5071melanomametastasiscell extravasationblood-brain barrier (BBB)endothelial junctions |
| spellingShingle | Federico Saltarin Adrian Wegmüller Leire Bejarano Ece Su Ildiz Pascale Zwicky Andréj Vianin Florentin Spadin Klara Soukup Vladimir Wischnewski Britta Engelhardt Urban Deutsch Ines J. Marques Martin Frenz Johanna A. Joyce Ruth Lyck Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation Cancers melanoma metastasis cell extravasation blood-brain barrier (BBB) endothelial junctions |
| title | Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation |
| title_full | Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation |
| title_fullStr | Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation |
| title_full_unstemmed | Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation |
| title_short | Compromised Blood-Brain Barrier Junctions Enhance Melanoma Cell Intercalation and Extravasation |
| title_sort | compromised blood brain barrier junctions enhance melanoma cell intercalation and extravasation |
| topic | melanoma metastasis cell extravasation blood-brain barrier (BBB) endothelial junctions |
| url | https://www.mdpi.com/2072-6694/15/20/5071 |
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