CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier
During parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB). The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesi...
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| Language: | English |
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MDPI AG
2014-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/15/5/8063 |
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| author | János Haskó Csilla Fazakas Judit Molnár Ádám Nyúl-Tóth Hildegard Herman Anca Hermenean Imola Wilhelm Yuri Persidsky István A. Krizbai |
| author_facet | János Haskó Csilla Fazakas Judit Molnár Ádám Nyúl-Tóth Hildegard Herman Anca Hermenean Imola Wilhelm Yuri Persidsky István A. Krizbai |
| author_sort | János Haskó |
| collection | DOAJ |
| description | During parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB). The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesis of leukocytes. Extravasation of leukocytes through the BBB is decreased by the activation of type 2 cannabinoid receptors (CB2); therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. First, we identified the presence of CB1, CB2(A), GPR18 (transcriptional variant 1) and GPR55 receptors in brain endothelial cells, while melanoma cells expressed CB1, CB2(A), GPR18 (transcriptional variants 1 and 2), GPR55 and GPR119. We observed that activation of CB2 receptors with JWH-133 reduced the adhesion of melanoma cells to the layer of brain endothelial cells. JWH-133 decreased the transendothelial migration rate of melanoma cells as well. Our results suggest that changes induced in endothelial cells are critical in the mediation of the effect of CB2 agonists. Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma. |
| first_indexed | 2024-04-13T18:31:59Z |
| format | Article |
| id | doaj.art-192c0195582447399030155ce6a925f7 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T18:31:59Z |
| publishDate | 2014-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-192c0195582447399030155ce6a925f72022-12-22T02:35:02ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-05-011558063807410.3390/ijms15058063ijms15058063CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain BarrierJános Haskó0Csilla Fazakas1Judit Molnár2Ádám Nyúl-Tóth3Hildegard Herman4Anca Hermenean5Imola Wilhelm6Yuri Persidsky7István A. Krizbai8Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, P.O. Box 521, Szeged H-6701, HungaryInstitute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, P.O. Box 521, Szeged H-6701, HungaryInstitute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, P.O. Box 521, Szeged H-6701, HungaryInstitute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, P.O. Box 521, Szeged H-6701, HungaryInstitute of Life Sciences, Vasile Goldis Western University of Arad, Arad 310414, RomaniaInstitute of Life Sciences, Vasile Goldis Western University of Arad, Arad 310414, RomaniaInstitute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, P.O. Box 521, Szeged H-6701, HungaryDepartment of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USAInstitute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, P.O. Box 521, Szeged H-6701, HungaryDuring parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB). The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesis of leukocytes. Extravasation of leukocytes through the BBB is decreased by the activation of type 2 cannabinoid receptors (CB2); therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. First, we identified the presence of CB1, CB2(A), GPR18 (transcriptional variant 1) and GPR55 receptors in brain endothelial cells, while melanoma cells expressed CB1, CB2(A), GPR18 (transcriptional variants 1 and 2), GPR55 and GPR119. We observed that activation of CB2 receptors with JWH-133 reduced the adhesion of melanoma cells to the layer of brain endothelial cells. JWH-133 decreased the transendothelial migration rate of melanoma cells as well. Our results suggest that changes induced in endothelial cells are critical in the mediation of the effect of CB2 agonists. Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.http://www.mdpi.com/1422-0067/15/5/8063blood-brain barrier (BBB)cerebral metastasismelanomacannabinoidCB2 |
| spellingShingle | János Haskó Csilla Fazakas Judit Molnár Ádám Nyúl-Tóth Hildegard Herman Anca Hermenean Imola Wilhelm Yuri Persidsky István A. Krizbai CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier International Journal of Molecular Sciences blood-brain barrier (BBB) cerebral metastasis melanoma cannabinoid CB2 |
| title | CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier |
| title_full | CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier |
| title_fullStr | CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier |
| title_full_unstemmed | CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier |
| title_short | CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier |
| title_sort | cb2 receptor activation inhibits melanoma cell transmigration through the blood brain barrier |
| topic | blood-brain barrier (BBB) cerebral metastasis melanoma cannabinoid CB2 |
| url | http://www.mdpi.com/1422-0067/15/5/8063 |
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