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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Expression of cannabinoid receptors and neurotrophins in human gliomas
C Calatozzolo1, A Salmaggi, B Pollo
1Department of Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
Abstract:
Recent studies have shown an anti-tumour activity of cannabinoid receptors CB1 and CB2 in gliomas. This effect was mediated by neurotrophins in breast and prostate carcinoma, while in gliomas this relationship has not yet been considered. The aim of this study was to investigate the expression of cannabinoid receptors CB1 and CB2, neurotrophin NGF and NT-3 and their receptors TrkA and TrkC in glioma and endothelial cells. The analysis was performed in 14 gliomas and 2 non-tumour brain specimens by immunohistochemistry and real-time quantitative-polymerase chain reaction (RTQ-PCR). Gliomas showed a weak immunoreactivity for CB1 and CB2 in tumour and in endothelial cells, and for NGF/TrkA mainly in tumour cells, while a moderate/diffuse immunoreactivity was found for NT-3/TrkC. CB2 was expressed on 3 out of 6 low-grade gliomas and in all high-grade gliomas. Non-tumour brain tissues were weakly positive in astrocytes and endothelium for CB1, CB2, NT-3 and TrkC and negative for NGF and TrkA. By RTQ-PCR, gliomas showed low mRNA levels of NGF/TrkA and moderate levels of CB1, NT-3 and TrkC. CB2 mRNA expression was low or absent. A potential role of cannabinoids, particularly of CB2 agonists devoid of psychotropic side effects, in glioma therapy could have a basis in glioblastomas, because they were all positive, though weakly, to CB2. The presence of neurotrophins and their receptors, mainly NT-3 and TrkC, suggests a possible role of these pathways in glioma growth/invasion, but further investigations are required to verify this hypothesis and a potential relationship between cannabinoids and neurotrophins.
Insights
This study explored cannabinoid receptors (CB1, CB2) and neurotrophins in gliomas. Findings suggest a potential therapeutic role for CB2 agonists in glioblastoma treatment.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Cannabinoid receptors CB1 and CB2 exhibit anti-tumour activity in various cancers.
- The role of neurotrophins in mediating cannabinoid anti-tumour effects is established in breast and prostate cancers.
- The relationship between cannabinoids and neurotrophins in gliomas remains under-investigated.
Purpose of the Study:
- To investigate the expression of cannabinoid receptors (CB1, CB2) and neurotrophins (NGF, NT-3) and their receptors (TrkA, TrkC) in glioma and endothelial cells.
- To explore potential links between cannabinoid signaling and neurotrophin pathways in glioma pathogenesis.
Main Methods:
- Immunohistochemistry and real-time quantitative-polymerase chain reaction (RTQ-PCR) were employed.
- Analysis was conducted on 14 gliomas and 2 non-tumour brain specimens.
- Expression levels of CB1, CB2, NGF, NT-3, TrkA, and TrkC were assessed.
Main Results:
- Gliomas showed weak CB1 and CB2 immunoreactivity, with CB2 present in all high-grade gliomas.
- Moderate/diffuse immunoreactivity for NT-3/TrkC was observed, while NGF/TrkA was mainly in tumour cells.
- RTQ-PCR revealed low mRNA for NGF/TrkA and moderate levels for CB1, NT-3, and TrkC; CB2 mRNA was low or absent.
Conclusions:
- CB2 receptor expression in glioblastomas suggests a potential therapeutic basis for CB2 agonists.
- Neurotrophins, particularly NT-3 and TrkC, may play a role in glioma growth and invasion.
- Further research is needed to confirm the relationship between cannabinoids and neurotrophins in gliomas.

