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

Haskó, János; Fazakas, Csilla; Molnár, J.; Nyúl‐Tóth, Ádám; Herman, Hildegard; Wilhelm, Imola; Persidsky, Yuri; Krizbai, István A.

doi:10.3390/ijms15058063

Cited by 31 publications

(23 citation statements)

References 49 publications

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“…Immune cells preponderantly express CB 2 . Consistent with this observation, there is a large body of data that supports a functional relevance for 2-AG as acting through CB 2 to inhibit migratory activities for a diverse array of immune cell types [74, 75]. Indeed, it has been suggested that 2-AG is the cognate functionally relevant eCB for CB 2 .…”

Section: Immune Systemmentioning

confidence: 71%

Endocannabinoid signaling at the periphery: 50 years after THC

Maccarrone

Bab

Bı́ró

et al. 2015

Trends in Pharmacological Sciences

561

549

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Fifty years ago (in 1964) the psychoactive ingredient of Cannabis sativa, Δ9-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide, AEA) in 1992, and 2-arachidonoylglycerol (2-AG) in 1995. Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize and degrade them, and that altogether form the eCB system. eCBs control basic biological processes, including cell-choice between survival and death, and progenitor/stem cell proliferation and differentiation. Not surprisingly, in the past two decades, eCBs have been recognized as key mediators of several aspects of human pathophysiology, and thus have emerged among the most widespread and versatile signaling molecules ever discovered. Here, some of the pioneers of this research field review the state-of-the-art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral eCB system for human health and disease pathogenesis, as well as to highlight emerging challenges and therapeutic hopes.

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Section: Immune Systemmentioning

confidence: 71%

Endocannabinoid signaling at the periphery: 50 years after THC

Maccarrone

Bab

Bı́ró

et al. 2015

Trends in Pharmacological Sciences

561

549

View full text Add to dashboard Cite

show abstract

“…Activation of CB1 and CB2 regulates cell migration and cytokine and chemokine production, with CB2 activation by 2-AG inhibiting migratory activities of immune cells [183,184]. AEA also inhibits production of proinflammatory cytokines, so that it reduces human monocyte interleukin (IL)-6 and IL-8 [185]; and IL-2, TNF-α and interferon (IFN)-γ from activated human T lymphocytes [186].…”

Section: Ecs and Immunoinflammatory System Dysregulationmentioning

confidence: 99%

Peripheral modulation of the endocannabinoid system in metabolic disease

Shrestha

Cuffe

Hutchinson

et al. 2018

Drug Discovery Today

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Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic disease. Cannabinoid receptor 1 (CB) is abundantly expressed in the brain but also expressed in the periphery. Cannabinoid receptor 2 (CB) is more abundant in the periphery, including the immune cells. In obesity, global antagonism of overexpressed CB reduces bodyweight but leads to centrally mediated adverse psychological outcomes. Emerging research in isolated cultured cells or tissues has demonstrated that targeting the endocannabinoid system in the periphery alleviates the pathologies associated with metabolic disease. Further, peripheral specific cannabinoid ligands can reverse aspects of the metabolic phenotype. This Keynote review will focus on current research on the functionality of peripheral modulation of the ECS for the treatment of obesity.

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“…Brain is considered a privileged site for the presence of blood brain barrier (BBB) protecting it against the entry of toxic substances and microorganisms [ 12 , 13 ]. Since the CNS also lacks the lymphatic system, the only way of metastatic cells to reach the brain is to cross this barrier [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Melanoma Cells Homing to the Brain: AnIn VitroModel

Rizzo

Vasco

Girgenti

et al. 2015

BioMed Research International

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We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The contact between astrocytes and HUVECs was demonstrated by electron microscopy: astrocytes endfeet pass through the 8.0 μm pores inducing HUVECs to assume a cerebral phenotype. Using this model we evaluated transmigration of melanoma cells from two different patients (M1 and M2) selected among seven melanoma primary cultures. M2 cells showed a statistically significant higher capability to pass across the in vitro BBB model, compared to M1. Expression of adhesion molecules was evaluated by flow cytometry: a statistically significant increased expression of MCAM, αvβ3, and CD49b was detected in M1. PCR array data showed that M2 had a higher expression of several matrix metalloproteinase proteins (MMPs) compared to M1. Specifically, data suggest that MMP2 and MMP9 could be directly involved in BBB permeability and that brain invasion by melanoma cells could be related to the overexpression of many MMPs. Future studies will be necessary to deepen the mechanisms of central nervous system invasion.

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

Cited by 31 publications

References 49 publications

Endocannabinoid signaling at the periphery: 50 years after THC

Endocannabinoid signaling at the periphery: 50 years after THC

Peripheral modulation of the endocannabinoid system in metabolic disease

Melanoma Cells Homing to the Brain: AnIn VitroModel

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