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Updated: Apr 16, 2026
Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting
Published on: September 25, 2012
Mouse low-grade gliomas contain cancer stem cells with unique molecular and functional properties
Yi-Hsien Chen1, Lucy D'Agostino McGowan1, Patrick J Cimino2
1Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
The availability of adult malignant glioma stem cells (GSCs) has provided unprecedented opportunities to identify the mechanisms underlying treatment resistance. Unfortunately, there is a lack of comparable reagents for the study of pediatric low-grade glioma (LGG). Leveraging a neurofibromatosis 1 (Nf1) genetically engineered mouse LGG model, we report the isolation of CD133(+) multi-potent low-grade glioma stem cells (LG-GSCs), which generate glioma-like lesions histologically similar to the parent tumor following injection into immunocompetent hosts. In addition, we demonstrate that these LG-GSCs harbor selective resistance to currently employed conventional and biologically targeted anti-cancer agents, which reflect the acquisition of new targetable signaling pathway abnormalities. Using transcriptomic analysis to identify additional molecular properties, we discovered that mouse and human LG-GSCs harbor high levels of Abcg1 expression critical for protecting against ER-stress-induced mouse LG-GSC apoptosis. Collectively, these findings establish that LGG cancer stem cells have unique molecular and functional properties relevant to brain cancer treatment.
Insights
Researchers isolated pediatric low-grade glioma stem cells (LG-GSCs) from a mouse model. These cells resist cancer treatments, offering new insights into brain cancer therapy and drug development.
Area of Science:
- Neuro-oncology
- Cancer Stem Cell Biology
Background:
- Adult malignant glioma stem cells (GSCs) aid treatment resistance research.
- Pediatric low-grade glioma (LGG) lacks comparable reagents for study.
Purpose of the Study:
- To isolate and characterize pediatric low-grade glioma stem cells (LG-GSCs).
- To investigate LG-GSC resistance mechanisms and identify therapeutic targets.
Main Methods:
- Utilized a neurofibromatosis 1 (Nf1) genetically engineered mouse LGG model.
- Isolated CD133(+) multi-potent LG-GSCs and assessed tumor formation in vivo.
- Performed transcriptomic analysis to identify molecular properties and resistance pathways.
Main Results:
- Successfully isolated functional LG-GSCs that form histologically similar tumors.
- Demonstrated LG-GSC resistance to conventional and targeted anti-cancer agents.
- Identified high Abcg1 expression in LG-GSCs, crucial for protecting against ER-stress-induced apoptosis.
Conclusions:
- Established LGG cancer stem cells possess unique molecular and functional properties.
- These properties are relevant for understanding and treating pediatric brain tumors.
- Findings highlight potential new therapeutic strategies targeting LGG stem cells.
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