Related Experiment Video
Updated: May 22, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Disrupting glioblastoma networks with tumor treating fields (TTFields) in in vitro models
Steffen Schlieper-Scherf1, Nils Hebach2,3, David Hausmann2,3
1Department of Neurosurgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Purpose:
This study investigates the biological effect of Tumor Treating Fields (TTFields) on key drivers of glioblastoma's malignancy-tumor microtube (TM) formation-and on the function and overall integrity of the tumor cell network.
Method:
Using a two-dimensional monoculture GB cell network model (2DTM) of primary glioblastoma cell (GBC) cultures (S24, BG5 or T269), we evaluated the effects of TTFields on cell density, interconnectivity and structural integrity of the tumor network. We also analyzed calcium (Ca2+) transient dynamics and network morphology, validating findings in patient-derived tumoroids and brain tumor organoids.
Results:
In the 2DTM assay, TTFields reduced cell density by 85-88% and disrupted network interconnectivity, particularly in cells with multiple TMs. A "crooked TM" phenotype emerged in 5-6% of treated cells, rarely seen in controls. Ca2+ transients were significantly compromised, with global Ca2+ activity reduced by 51-83%, active and periodic cells by over 50%, and intercellular co-activity by 52% in S24, and almost completely in BG5 GBCs. The effects were more pronounced at 200 kHz compared to a 50 kHz TTFields. Similar reductions in Ca2+ activity were observed in patient-derived tumoroids. In brain tumor organoids, TTFields significantly reduced tumor cell proliferation and infiltration.
Conclusion:
Our comprehensive study provides new insights into the multiple effects of Inovitro-modeled TTFields on glioma progression, morphology and network dynamics in vitro. Future in vivo studies to verify our in vitro findings may provide the basis for a deeper understanding and optimization of TTFields as a therapeutic modality in the treatment of GB.
Insights
Tumor Treating Fields (TTFields) disrupt glioblastoma cell networks and tumor microtube formation. These fields significantly reduce cell density, interconnectivity, and calcium signaling, offering new therapeutic insights.
Area of Science:
- Oncology
- Biophysics
- Cancer Biology
Background:
- Glioblastoma (GB) is a highly aggressive brain tumor.
- Tumor microtube (TM) formation is crucial for glioblastoma network integrity and progression.
- Understanding the biological effects of Tumor Treating Fields (TTFields) is vital for optimizing glioblastoma treatment.
Purpose of the Study:
- To investigate the biological effects of TTFields on TM formation in glioblastoma.
- To assess the impact of TTFields on glioblastoma cell network function and integrity.
- To analyze the influence of TTFields on calcium signaling within glioblastoma networks.
Main Methods:
- Utilized a two-dimensional monoculture glioblastoma cell network model (2DTM) with primary glioblastoma cell cultures (GBCs).
- Evaluated TTFields' effects on cell density, interconnectivity, and network structural integrity.
- Analyzed calcium (Ca2+) transient dynamics and network morphology, with validation in patient-derived tumoroids and brain tumor organoids.
Main Results:
- TTFields significantly reduced GBC density (85-88%) and disrupted network interconnectivity.
- A 'crooked TM' phenotype was observed in treated cells; Ca2+ transients were compromised, reducing global activity (51-83%) and intercellular co-activity.
- Effects were more pronounced at 200 kHz; similar Ca2+ activity reductions were seen in tumoroids, and TTFields reduced proliferation and infiltration in brain tumor organoids.
Conclusions:
- TTFields exhibit multiple in vitro effects on glioma progression, morphology, and network dynamics.
- These findings provide novel insights into TTFields' mechanisms against glioblastoma.
- Further in vivo studies are warranted to validate these in vitro results for therapeutic optimization.
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