期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 15, 期 5, 页码 8063-8074出版社
MDPI
DOI: 10.3390/ijms15058063
关键词
blood-brain barrier (BBB); cerebral metastasis; melanoma; cannabinoid; CB2
资金
- Hungarian Research Fund [OTKA PD-100958, K-100807]
- National Development Agency (Hungary-Romania Cross-Border Co-operation Programme) [HURO/1101/173/2.2.1, TAMOP-4.2.2.A-11/1/KONV-2012-0052]
- Janos Bolyai Research Fellowship of the Hungarian Academy of Sciences [BO/00320/12/8]
- [POSDRU/159/1.5/S/133391]
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.
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