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Updated: Jun 13, 2026
A Human Glioblastoma Organotypic Slice Culture Model for Study of Tumor Cell Migration and Patient-specific Effects of Anti-Invasive Drugs
Published on: July 20, 2017
The side population of gliomas exhibits decreased cell migration
Kathrin Weber1, Werner Paulus, Volker Senner
1Institute of Neuropathology, University Hospital Munster, Munster, Germany.
Abstract:
Side population (SP) cells identified using the Hoechst 33342 fluorescent dye efflux technique overlap with the tumor stem cell fraction that is responsible for tumorigenesis and recurrence in malignant gliomas. Because diffuse invasion of glioma cells represents the main obstacle to successful therapy and underlies recurrence, we examined the existence of an SP fraction in 8 human glioma cell lines and in a sample of primary glioblastoma (GBM) cells and compared the migration potential of SP cells with that of non-SP cells. The SP cells were detected in U373MG (1.5%), U87MG (1.9%), H4 (2.2%), and primary GBM cells (1.5%). The SP cells displayed approximately 2-fold higher expression of ABCG2, the transporter that is mainly responsible for dye efflux. In monolayer and transwell assays, the migration of SP cells was lower than that of non-SP cells. Furthermore, there was a distinct SP in GBM cells selected for slow migration but not in their fast counterparts. The finding that SP cells have a lower migration potential than non-SP cells suggests that cells underlying the initiation and recurrence of gliomas are able to migrate, albeit less so than other glioma cells. These data may also provide an explanation for the clinical observation that most GBM recur in close proximity to the site of the original tumor.
Insights
Malignant glioma recurrence is linked to side population (SP) cells. These SP cells, responsible for tumor initiation, show lower migration potential than non-SP cells, explaining localized tumor regrowth.
Area of Science:
- Neuro-oncology
- Cancer Stem Cells
- Cell Biology
Background:
- Malignant gliomas, particularly glioblastoma (GBM), are characterized by diffuse invasion, posing a therapeutic challenge.
- Tumorigenesis and recurrence in gliomas are attributed to a fraction of tumor stem cells.
- Side population (SP) cells, identified by Hoechst 33342 dye efflux, are implicated as tumor stem cells in gliomas.
Purpose of the Study:
- To investigate the presence and migratory potential of SP cells in human glioma cell lines and primary GBM.
- To compare the migration capabilities of SP cells versus non-SP cells in gliomas.
Main Methods:
- Utilized the Hoechst 33342 fluorescent dye efflux technique to identify SP cells.
- Analyzed 8 human glioma cell lines and primary GBM samples.
- Performed monolayer and transwell migration assays to compare SP and non-SP cell migration.
- Quantified ABCG2 transporter expression in SP cells.
Main Results:
- SP cells were detected in several glioma cell lines (U373MG, U87MG, H4) and primary GBM, with varying percentages.
- SP cells exhibited approximately 2-fold higher expression of the ABCG2 transporter.
- SP cells demonstrated significantly lower migration potential in both monolayer and transwell assays compared to non-SP cells.
- A distinct SP fraction was observed in slow-migrating GBM cells, but not in fast-migrating counterparts.
Conclusions:
- Glioma SP cells, implicated in tumor initiation and recurrence, possess lower migratory capacity than non-SP cells.
- This reduced migration of SP cells may explain the localized recurrence patterns observed clinically in GBM.
- The findings suggest a complex interplay between stemness properties and cell migration in glioma progression.
