Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling
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 pare...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/95971 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/95971 |
| Access Level: | acceso abierto |
| Palabra clave: | 616-006.04 Cannabinoid receptor Endocannabinoid system Melanoma Brain metastasis Glutamate NMDA receptor Cell proliferation Oncología Ciencias Biomédicas 3207 Patología 3207.13 Oncología |
| Sumario: | 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 glutamate release, 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. |
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