A novel 3D in vitro model of glioblastoma reveals resistance to temozolomide which was potentiated by hypoxia
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 CONCLUSIONCitation
Musah-Eroje A, Watson S (2019) 'A novel 3D in vitro model of glioblastoma reveals resistance to temozolomide which was potentiated by hypoxia', Journal of Neuro-Oncology, 142 (2), pp.231-240.Publisher
SpringerJournal
Journal of Neuro-OncologyPubMed ID
30694423PubMed Central ID
PMC6449313Additional Links
https://link.springer.com/article/10.1007/s11060-019-03107-0Type
ArticleLanguage
enISSN
0167-594XEISSN
1573-7373ae974a485f413a2113503eed53cd6c53
10.1007/s11060-019-03107-0
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