| Autor: |
Lah TT; Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia.; Jožef Stefan International Postgraduate School, Nanosciences and Nanotechnologies, 1000 Ljubljana, Slovenia., Majc B; Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia.; Jožef Stefan International Postgraduate School, Nanosciences and Nanotechnologies, 1000 Ljubljana, Slovenia., Novak M; Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia., Sušnik A; Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia., Breznik B; Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia., Porčnik A; Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia., Bošnjak R; Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia., Sadikov A; Faculty of Computer and Information Science, University of Ljubljana, 1000 Ljubljana, Slovenia., Malavolta M; Faculty of Computer and Information Science, University of Ljubljana, 1000 Ljubljana, Slovenia., Halilčević S; Faculty of Computer and Information Science, University of Ljubljana, 1000 Ljubljana, Slovenia., Mlakar J; Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia., Zomer R; MGC Pharmaceuticals d.o.o., 1000 Ljubljana, Slovenia. |
| Abstrakt: |
Glioblastoma (GBM) is one of the most aggressive cancers, comprising 60-70% of all gliomas. The large G-protein-coupled receptor family includes cannabinoid receptors CB1, CB2, GPR55, and non-specific ion receptor protein transporters TRPs. First, we found up-regulated CNR1, GPR55 , and TRPV1 expression in glioma patient-derived tissue samples and cell lines compared with non-malignant brain samples. CNR1 and GPR55 did not correlate with glioma grade, whereas TRPV1 negatively correlated with grade and positively correlated with longer overall survival. This suggests a tumour-suppressor role of TRPV1 . With respect to markers of GBM stem cells, preferred targets of therapy, TRPV1 and GPR55 , but not CNR1 , strongly correlated with different sets of stemness gene markers: NOTCH, OLIG2, CD9, TRIM28 , and TUFM and CD15 , SOX2, OCT4 , and ID1 , respectively. This is in line with the higher expression of TRPV1 and GPR55 genes in GSCs compared with differentiated GBM cells. Second, in a panel of patient-derived GSCs, we found that CBG and CBD exhibited the highest cytotoxicity at a molar ratio of 3:1. We suggest that this mixture should be tested in experimental animals and clinical studies, in which currently used Δ9-tetrahydrocannabinol (THC) is replaced with efficient and non-psychoactive CBG in adjuvant standard-of-care therapy. |
