# Glioma chemotherapeutic resistance is tied to membrane electrophysiological properties and glycosylation

**Authors:** Alan Y. L. Jiang, Andrew R. Yale, J. Nicole Hanamoto, Nicole S. Lav, Vi Phuong Dang, Clarissa C. Ro, Christopher R. Douglas, Kaijun Di, Jacob Deyell, Daniela A. Bota, Lisa A. Flanagan

PMC · DOI: 10.1002/btm2.70069 · Bioengineering & Translational Medicine · 2025-09-22

## TL;DR

This study shows that glioma cells resistant to chemotherapy have distinct membrane properties and glycosylation patterns, which could help develop better treatment strategies.

## Contribution

The paper identifies electrophysiological and glycosylation properties of the plasma membrane as predictors of chemotherapeutic resistance in glioma cells.

## Key findings

- TMZ-resistant glioma cells show significant differences in plasma membrane glycosylation.
- Electrophysiological properties of the membrane can predict TMZ resistance in glioma cells.
- Sorting cells by membrane properties enriches for TMZ-resistant populations.

## Abstract

Diffuse gliomas are brain tumors that include oligodendroglioma, astrocytoma, and glioblastoma (GBM), the most common and deadly primary brain tumor. A major challenge in glioma treatment is resistance to the first‐line chemotherapeutic, temozolomide (TMZ). Plasma membrane properties of cells with increased chemotherapeutic resistance are not well understood, despite the fact that the membrane is the first point of contact with the environment and greatly shapes cell behavior. Plasma membrane glycosylation impacts cell function, and we found significant differences in glycosylation of TMZ‐resistant cells. We further identified plasma membrane electrophysiological properties predicting glioma cell TMZ resistance. We enriched cells with higher TMZ resistance by sorting glioma cells based on electrophysiological properties, indicating the relevance of membrane properties to chemotherapeutic resistance. These findings could lead to rapid separation methods for patient tumor cells, a better understanding of the molecular profiles of resistant cells, and novel treatment options for gliomas.

## Linked entities

- **Chemicals:** temozolomide (PubChem CID 5394), TMZ (PubChem CID 5394)
- **Diseases:** glioma (MONDO:0021042), oligodendroglioma (MONDO:0002540), astrocytoma (MONDO:0019781), glioblastoma (MONDO:0018177), GBM (MONDO:0018177)

## Full-text entities

- **Diseases:** Diffuse gliomas (MESH:D005910), GBM (MESH:D005909), brain tumor (MESH:D001932), tumor (MESH:D009369), oligodendroglioma (MESH:D009837), astrocytoma (MESH:D001254)
- **Chemicals:** TMZ (MESH:D000077204)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12821226/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12821226/full.md

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Source: https://tomesphere.com/paper/PMC12821226