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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
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Tumor-Derived Membrane Vesicles Restrain Migration in Gliomas By Altering Collective Polarization.
Megha Jhunjhunwala1, Lin-Sheng Yu1, Ping-Chen Kuo1
1National Tsing Hua University, Hsinchu 300044, Republic of China.
ACS Applied Bio Materials
|October 20, 2023
Summary
Cell membrane vesicles (CMVs) regulate collective cell behavior. Glioma-derived CMVs reduced glioma cell migration and invasion, suggesting potential as adjuvant cancer therapy.
Area of Science:
- Biomedical Engineering
- Cellular Mechanobiology
- Cancer Research
Background:
- Mechanobiology's role in biomedical applications is underdeveloped.
- Cell membrane vesicles (CMVs) are utilized as nanodrug carriers.
- Gliomas are aggressive brain tumors with poor patient survival rates.
Purpose of the Study:
- To investigate the use of CMVs as tactile cues for mechano-regulation of collective cell behaviors.
- To explore the potential of glioma-derived CMVs in modulating glioma cell mechanics and behavior.
- To assess the therapeutic implications of CMVs in glioma treatment.
Main Methods:
- Utilized glioma- and microglia-derived CMVs as tactile cues.
- Quantified traction stress and cell migration speed of glioma cell collectives.
- Employed the cellular Potts model to elucidate migration speed changes.
- Analyzed intracellular force modulation, cytoskeletal reorganization, and drug diffusion.
Main Results:
- CMV application doubled glioma cell traction stress with increased concentration.
- Glioma-CMVs constrained cell protrusions, reducing collective migration speed by ~40%.
- Glioma-CMVs downregulated YAP-1, altered drug diffusion, and enhanced apoptosis in glioma spheroids.
Conclusions:
- Glioma-derived CMVs can regulate collective cell mechanics and behavior.
- CMVs show potential as an adjuvant therapy to restrict tumor invasion and improve reagent penetration.
- Regulating cell mechanics via CMVs offers a foundation for novel therapeutic strategies in cancer.
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