Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Interrogation of GDC-TCGA Melanoma Datasets
2.2. Cells
2.3. Quantitative PCR
2.4. Cell Viability Assays
2.5. Immunofluorescence
2.6. Animals
2.7. Tumour Allografts
2.8. Magnetic Resonance Imaging (MRI)
2.9. Western Blotting
2.10. Intracarotid Artery Injection
2.11. Brain Metastatic Burden Analysis
2.12. Tail Vein Injection
3. Results
3.1. Dysregulation of ECS Elements and Glutamate Receptors in Melanoma Metastases
3.2. Blockade of NMDARs Inhibits Melanoma Cell Proliferation In Vitro
3.3. CB1Rs Located on Glutamatergic Neurons Control the Growth of MBMs In Vivo
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Forward Primer (5′–3′) | Reverse Primer (5′–3′) |
---|---|---|
GRIA1 | ACCACTACATCCTCGCCAAC | TCACTTGTCCTCCACTGCTG |
GRIA2 | ATTCTGCATGCTCCCACCTA | TTCTAAAACTTGCTTTTCAGGCTAT |
GRIA3 | AGCCGTGTGATACGATGAAA | CAAGGTTTACAGGCGTTCCT |
GRIA4 | CTGCCAACAGTTTTGCTGTG | AAATGGCAAACACCCCTCTA |
GRIN1 | GCTTTTGCAGCCGTGAAC | GGGCTCTGCTCTACCACTCTT |
GRIN2A | ATTCAACCAGAGGGGCGTA | TTCAAGACAGCTGCGTCATAG |
GRIN2B | CTTCCTCCTTGCTTTCCACTT | GGTGAGAAAAGCCAACCTGA |
GRIN2C | AGTTCGGGGGACAGACAAG | TCTCATGGCCAGAATTTCAA |
GRIN2D | TGCGATACAACCAGCCAAG | AGATGAAGGCGTCCAGTTTC |
GRM1 | GCCCAATGCAGAGCTCAC | GTCACTCCACTCGAGGTAACG |
GRM2 | GATGTCTCCATCCAGGTGGC | AGCCTACCTTCTGGTAGCGA |
GRM8 | CTGATATGGAGCTGCGGGT | CATGGGGGAAGGCTTTAGGG |
DLG4 | GCCAATTCTCCCCCTGTGAT | CGTTCACCTGCAACTCATATCC |
DLGAP1 | CAGCACACATCCAACTTGCC | CAACAGCAATCGCAGTCCG |
Gene | 1014 | YUMM 1.7 | B16.F10 |
---|---|---|---|
GRIN1 | 33.29 ± 1.30 | 31.84 ± 0.02 | 27.62 ± 0.62 |
GRIN2A | 33.45 ± 1.28 | 27.78 ± 0.94 | N.D. |
GRIN2B | 30.01 ± 1.53 | 28.15 ± 1.41 | 27.55 ± 1.87 |
GRIN2C | 30.20 ± 1.11 | 28.77 ± 2.31 | 29.18 ± 1.12 |
GRIN2D | 32.88 ± 1.48 | 26.84 ± 1.30 | 31.00 ± 0.08 |
GRIA1 | 34.59 ± 2.41 | 31.72 ± 1.10 | 35.40 ± 3.44 |
GRIA2 | 30.79 ± 1.87 | 28.66 ± 1.10 | 30.17 ± 2.09 |
GRIA3 | N.D. | N.D. | N.D. |
GRIA4 | 24.62 ± 2.57 | 33.81 ± 1.23 | 26.86 ± 0.80 |
GRM1 | 29.15 ± 1.60 | 32.41 ± 2.02 | 30.08 ± 0.58 |
GRM2 | N.D. | N.D. | N.D. |
GRM8 | 37.72 ± 1.88 | 33.55 ± 2.46 | 31.31 ± 1.41 |
DLG4 | 23.57 ± 2.88 | 20.98 ± 3.38 | 25.25 ± 0.31 |
DLGAP1 | 34.65 ± 2.12 | 29.81 ± 8.80 | 36.86 ± 2.04 |
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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. https://doi.org/10.3390/cancers15092439
Costas-Insua C, Seijo-Vila M, Blázquez C, Blasco-Benito S, Rodríguez-Baena FJ, 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(9):2439. https://doi.org/10.3390/cancers15092439
Chicago/Turabian StyleCostas-Insua, Carlos, Marta Seijo-Vila, Cristina Blázquez, Sandra Blasco-Benito, Francisco Javier Rodríguez-Baena, Giovanni Marsicano, Eduardo Pérez-Gómez, Cristina Sánchez, Berta Sánchez-Laorden, and Manuel Guzmán. 2023. "Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling" Cancers 15, no. 9: 2439. https://doi.org/10.3390/cancers15092439