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A novel 3D in vitro model of glioblastoma reveals resistance to temozolomide which was potentiated by hypoxia

  • Ahmed Musah-Eroje
    ,
  • Sue Watson
  • University of Nottingham
Research Output: Contribution to journal Article Peer-review

Open access

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

Abstract

Glioblastoma (GBM) is the most common invasive malignant brain tumour in adults. It is traditionally investigated in vitro by culturing cells as a monolayer (2D culture) or as neurospheres (clusters enriched in cancer stem cells) but neither system accurately reflects the complexity of the three-dimensional (3D) chemoresistant microenvironment of GBM. Using three GBM cell-lines (U87, U251, and SNB19), the effect of culturing cells in a Cultrex-based basement membrane extract (BME) [3D Tumour Growth Assay (TGA)] on morphology, gene expression, metabolism, and temozolomide chemoresistance was investigated. Cells were easily harvested from the 3D model and cultured as a monolayer (2D) and neurospheres. Indeed, the SNB19 cells formed neurospheres only after they were first cultured in the 3D model. The expression of CD133 and OCT4 was upregulated in the neurosphere and 3D assays respectively. Compared with cells cultured in the 2D model, cells were more resistant to temozolomide in the 3D model and this resistance was potentiated by hypoxia. Taken together, these results suggest that micro-environmental factors influence GBM sensitivity to temozolomide. Knowledge of the mechanisms involved in temozolomide resistance in this 3D model might lead to the identification of new strategies that enable the more effective use of the current standard of care agents. PURPOSE MATERIALS AND METHODS RESULTS CONCLUSION

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 231-240

Journal (Volume, Issue Number)

Journal of Neuro-Oncology (Volume 142, Issue 2)

Publication milestones

  • Published - 29/01/2019

Publication status

Published - 29/01/2019

ISSN

0167-594X

External Publication IDs

  • handle.net: 10547/623624
  • Scopus: 85061001251

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