RT Journal Article
T1 Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling
A1 Costas Insúa, Carlos
A1 Seijo Vila, Marta
A1 Blázquez Ortiz, Cristina
A1 Blasco Benito, Sandra
A1 Rodríguez Baena, Francisco Javier
A1 Marsicano, Giovanni
A1 Pérez Gómez, Eduardo
A1 Sánchez García, María Cristina
A1 Sánchez Laorden, Berta
A1 Guzmán Pastor, Manuel
AB An estimated 60% of melanoma patients develop melanoma brain metastases(MBMs). However, the molecular factors that govern the growth of MBMs are still unknown. The excitatory neurotransmitter glutamate has been shown to control the proliferation of various types of cancer cells within the brain parenchyma, but the cellular sources and molecular mechanisms involved in this process remain unclear. By their well-known role in inhibiting synaptic glutamaterelease, cannabinoid CB1 receptors (CB1Rs) located on glutamatergic nerve terminals are conceivably well-positioned to control the growth of MBMs. In silico data mining in cancer-genome atlases and in vitro studies with melanoma cell lines supported that a glutamate-NMDA receptor axis drives melanoma cell proliferation. Strikingly, grafting melanoma cells into the brain of mice lacking CB1Rs selectively in glutamatergic neurons increased tumour size and concomitantly activated NMDA receptors on tumour cells. Altogether, our findings reveal an unprecedented role of neuronal CB1Rs in controlling MBMs.
PB MDPI
SN 2072-6694
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/95971
UL https://hdl.handle.net/20.500.14352/95971
LA eng
NO Costas-Insua, C.; Seijo-Vila, M.; Blázquez, C.; Blasco-Benito, S.; Rodríguez-Baena, F.J.; Marsicano, G.; Pérez-Gómez, E.; Sánchez, C.; Sánchez-Laorden, B.; Guzmán, M. Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling. Cancers 2023, 15, 2439.
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO European Commission
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 6 abr 2025