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Updated: May 20, 2026
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
MGMT hypermethylation and MDR system in glioblastoma cancer stem cells
Valentina Caldera1, Marta Mellai, Laura Annovazzi
1Neuro-bio-oncology Center, Policlinico di Monza Foundation (Vercelli)/Consortium of Neurosciences, University of Pavia, Italy.
Background:
Cancer stem cells (CSCs) in gliomas are associated with resistance to radio- and chemotherapy, based on O(6)-methylguanine-DNA methyltransferase (MGMT) hypermethylation and the Multidrug resistance (MDR) system activation.
Materials And Methods:
Samples from 21 glioblastomas (GBMs) were put in culture with growth factors or serum in order to obtain neurospheres or adherent cells. Both were genetically and immunohistochemically characterized for ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), ATP-binding cassette, sub-family C (CFTR/MRP), member 1 (ABCC1) and MGMT expression together with primary tumors.
Results:
ABCB1 expression was positive in endothelial cells of primary tumors. ABCC1 expression was variably positive in tumor cells and positive in neurospheres, and less expressed in adherent cells. MGMT was methylated and unmethylated in primary tumors and in neurospheres, respectively, and unmethylated in adherent cells.
Conclusion:
Methylation is an epigenetic event affecting progenitors before the separation of the two glia lineages and maximally the future initiating cells. ABCB1 expression is limited to endothelial cells, whereas ABCC1 expression could mark a minority of tumor cells approaching a stem-like status.
Insights
Cancer stem cells in gliomas exhibit resistance to treatment due to O(6)-methylguanine-DNA methyltransferase (MGMT) hypermethylation and multidrug resistance (MDR) activation. ABCC1 expression may indicate a stem-like status in some glioma cells.
Area of Science:
- Neuroscience
- Oncology
- Molecular Biology
Background:
- Cancer stem cells (CSCs) drive glioma resistance to radio- and chemotherapy.
- This resistance is linked to O(6)-methylguanine-DNA methyltransferase (MGMT) hypermethylation and Multidrug Resistance (MDR) system activation.
Purpose of the Study:
- To investigate the expression of drug resistance markers in glioblastoma (GBM) cells.
- To characterize neurospheres and adherent cells derived from GBMs for specific gene expressions.
Main Methods:
- Cultured GBM samples (n=21) to generate neurospheres and adherent cells.
- Performed genetic and immunohistochemical characterization for ABCB1, ABCC1, and MGMT expression.
- Compared marker expression in cultured cells with primary tumors.
Main Results:
- ABCB1 expression was observed in endothelial cells of primary tumors.
- ABCC1 expression was variable in tumor cells, positive in neurospheres, and reduced in adherent cells.
- MGMT was methylated in primary tumors but unmethylated in both neurospheres and adherent cells.
Conclusions:
- Epigenetic methylation affects glial progenitors before lineage separation, impacting future initiating cells.
- ABCB1 expression is restricted to endothelial cells.
- ABCC1 expression may identify a subset of glioma cells with stem-like characteristics.
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