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Int. J. Mol. Sci. 2014, 15(5), 8063-8074; doi:10.3390/ijms15058063

CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier

1, 2
1 Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, P.O. Box 521, Szeged H-6701, Hungary 2 Institute of Life Sciences, Vasile Goldis Western University of Arad, Arad 310414, Romania 3 Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA
* Author to whom correspondence should be addressed.
Received: 31 March 2014 / Revised: 4 April 2014 / Accepted: 22 April 2014 / Published: 8 May 2014
(This article belongs to the Special Issue Brain Metastasis 2014)
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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.
Keywords: blood-brain barrier (BBB); cerebral metastasis; melanoma; cannabinoid; CB2 blood-brain barrier (BBB); cerebral metastasis; melanoma; cannabinoid; CB2
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Haskó, J.; Fazakas, C.; Molnár, J.; Nyúl-Tóth, Á.; Herman, H.; Hermenean, A.; Wilhelm, I.; Persidsky, Y.; Krizbai, I.A. CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier. Int. J. Mol. Sci. 2014, 15, 8063-8074.

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