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Updated: May 16, 2026
12:52
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Mesenchymal high-grade glioma is maintained by the ID-RAP1 axis
Francesco Niola1, Xudong Zhao, Devendra Singh
1Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA.
The Journal of Clinical Investigation
|December 18, 2012
Summary
Inactivating ID proteins in high-grade gliomas (HGGs) causes glioma-initiating cells (GICs) to detach from their niche, leading to tumor regression. This suggests targeting ID proteins could be a novel therapeutic strategy for these aggressive brain tumors.
Area of Science:
- Neuro-oncology
- Cancer Stem Cell Biology
- Molecular Oncology
Background:
- High-grade gliomas (HGGs) are aggressive brain tumors driven by glioma-initiating cells (GICs).
- GICs rely on the perivascular niche for self-renewal and differentiation, contributing to tumor aggressiveness.
- ID proteins are implicated in maintaining stemness and niche anchorage of GICs.
Purpose of the Study:
- To investigate the therapeutic potential of inactivating ID proteins in HGG.
- To model the effects of ID gene ablation on GICs and tumor progression in a mesenchymal HGG mouse model.
Main Methods:
- Selective ablation of Id genes in tumor cells within a novel mouse model of human mesenchymal HGG.
- Analysis of GIC release from the perivascular niche and subsequent tumor regression.
- Investigation of the molecular mechanisms involving Rap1gap and RAP1 in GIC displacement.
- Identification of an ID pathway gene signature for patient stratification.
Main Results:
- Deletion of three Id genes led to rapid GIC release from the perivascular niche and significant tumor regression.
- GIC displacement was mediated by the Rap1gap/RAP1 signaling pathway, affecting cell adhesion.
- A 5-gene ID pathway signature identified two glioma patient subgroups with distinct clinical outcomes.
Conclusions:
- ID protein activity is crucial for maintaining mesenchymal HGG by anchoring GICs to their niche.
- Pharmacological inactivation of ID proteins represents a promising therapeutic strategy for HGG.
- The identified gene signature may aid in stratifying patients for targeted therapies.
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