ORCID
- Hanemann, Oliver: 0000-0002-1951-1025
Abstract
Meningiomas are the most common intracranial brain tumours. These tumours are heterogeneous and encompass a wide spectrum of clinical aggressivity. Treatment options are limited to surgery and radiotherapy and have a risk of post-operative morbidities and radiation neurotoxicity, reflecting the need for new therapies. Three-dimensional (3D) patient-derived cell culture models have been shown to closely recapitulate in vivo tumour biology, including microenvironmental interactions and have emerged as a robust tool for drug development. Here, we established a novel easy-to-use 3D patient-derived meningioma spheroid model using a scaffold-free approach. Patient-derived meningioma spheroids were characterised and compared to patient tissues and traditional monolayer cultures by histology, genomics, and transcriptomics studies. Patient-derived meningioma spheroids closely recapitulated morphological and molecular features of matched patient tissues, including patient histology, genomic alterations, and components of the immune microenvironment, such as a CD68 + and CD163 + positive macrophage cell population. Comprehensive transcriptomic profiling revealed an increase in epithelial-to-mesenchymal transition (EMT) in meningioma spheroids compared to traditional monolayer cultures, confirming this model as a tool to elucidate EMT in meningioma. Therefore, as proof of concept study, we developed a treatment strategy to target EMT in meningioma. We found that combination therapy using the MER tyrosine kinase (MERTK) inhibitor UNC2025 and the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) effectively decreased meningioma spheroid viability and proliferation. Furthermore, we demonstrated this combination therapy significantly increased the expression of the epithelial marker E-cadherin and had a repressive effect on WHO grade 2-derived spheroid invasion, which is suggestive of a partial reversal of EMT in meningioma spheroids.
DOI
10.1186/s40478-023-01677-9
Publication Date
2023-12-15
Publication Title
Acta neuropathologica communications
Volume
11
Issue
1
Embargo Period
2024-01-27
Organisational Unit
Peninsula Medical School
Recommended Citation
van, d. W., Ercolano, E., Zhang, T., Shah, M., Banton, M., Na, J., Adams, C., Hilton, D., Kurian, K., & Hanemann, C. (2023) 'A novel patient-derived meningioma spheroid model as a tool to study and treat epithelial-to-mesenchymal transition (EMT) in meningiomas', Acta neuropathologica communications, 11(1). Available at: https://doi.org/10.1186/s40478-023-01677-9
