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A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies
Published on: November 7, 2015
Distinctive pattern of cannabinoid receptor type II (CB2) expression in adult and pediatric brain tumors
Aleksandra Ellert-Miklaszewska1, Wieslawa Grajkowska, Konrad Gabrusiewicz
1Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Poland.
Abstract:
The efficacy of cannabinoids against high-grade glioma in animal models, mediated by two specific receptors, CB1 and CB2, raised promises for targeted treatment of the most frequent and malignant primary brain tumors. Unlike the abundantly expressed CB1, the CB2 receptor shows a restricted distribution in normal brain. Although brain tumors constitute the second most common malignancy in children and the prevalence of histological types of brain tumors vary significantly between the adult and pediatric populations, cannabinoid receptor expression in pediatric tumors remains unknown. In the present study, we compared the expression of the CB2 receptor in paraffin-embedded sections from primary brain tumors of adult and pediatric patients. Most glioblastomas expressed very high levels of CB2 receptors and the expression correlated with tumor grade. Interestingly, some benign pediatric astrocytic tumors, such as subependymal giant cell astrocytoma (SEGA), which may occasionally cause mortality owing to progressive growth, also displayed high CB2 immunoreactivity. The high levels of CB2 expression would predestine those tumors to be vulnerable to cannabinoid treatment. In contrast, all examined cases of embryonal tumors (medulloblastoma and S-PNET), the most frequently diagnosed malignant brain tumors in childhood, showed no or trace CB2 immunoreactivity. Our results suggest that the CB2 receptor expression depends primarily on the histopathological origin of the brain tumor cells and differentiation state, reflecting the tumor grade.
Insights
Cannabinoid receptor CB2 is highly expressed in adult and pediatric high-grade gliomas, suggesting potential for targeted cannabinoid therapies. However, pediatric embryonal tumors show minimal CB2 expression.
Area of Science:
- Neuro-oncology
- Molecular biology
- Pharmacology
Background:
- Cannabinoids show efficacy against high-grade glioma in animal models via CB1 and CB2 receptors.
- CB2 receptor has restricted distribution in normal brain, unlike CB1.
- Pediatric brain tumors are common, but cannabinoid receptor expression is largely unknown.
Purpose of the Study:
- To compare CB2 receptor expression in adult and pediatric brain tumors.
- To investigate the potential of CB2 receptor as a therapeutic target in pediatric brain tumors.
Main Methods:
- Immunohistochemical analysis of CB2 receptor expression.
- Comparison of CB2 expression in paraffin-embedded sections of adult and pediatric brain tumors.
- Correlation of CB2 expression with tumor grade and histopathology.
Main Results:
- High CB2 receptor expression was observed in most glioblastomas, correlating with tumor grade.
- Benign pediatric astrocytic tumors (SEGA) also showed high CB2 immunoreactivity.
- Embryonal tumors (medulloblastoma, S-PNET) demonstrated no or trace CB2 expression.
Conclusions:
- CB2 receptor expression in brain tumors is dependent on histopathological origin and differentiation state.
- High CB2 expression in certain gliomas suggests vulnerability to cannabinoid treatment.
- Lack of CB2 expression in pediatric embryonal tumors indicates limited therapeutic potential for cannabinoids in these specific cancers.
