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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
Silencing of Eps8 blocks migration and invasion in human glioblastoma cell lines
Maria Grazia Cattaneo1, Elisa Cappellini, Lucia M Vicentini
1Department of Pharmacology, School of Medicine, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milano, Italy.
Abstract:
Glioblastoma multiforme (GBM) is the most malignant human primary brain tumor, and its infiltrative nature represents the leading cause for the failure of therapies and tumor recurrences. It is therefore crucial the knowledge of the molecular mechanisms underlying GBM invasion to identify novel therapeutic targets to limit motility. In this study, we evaluated the role of Epidermal growth factor receptor Pathway Substrate 8 (Eps8), a crucial regulator of the actin cytoskeleton dynamics accompanying cell motility and invasion, in GBM migration and invasiveness. We found that silencing of the protein by small interfering RNAs (siRNAs) abrogated the migratory and invasive capacity of three different human GBM cell lines both in 2-dimensional (2-D) and 3-dimensional (3-D) in vitro assays. The inhibitory effect on invasion was maintained independently by the migration mode utilized by the cells in our 3-D model, and was accompanied by an impaired formation of actin-based cytoskeletal protrusive structures. Our data propose Eps8 as a key molecule involved in the control of the intrinsic invasive behavior of GBM cells, and suggest that this protein might represent a useful target for the design of new drugs for the treatment of these tumors.
Insights
Epidermal growth factor receptor Pathway Substrate 8 (Eps8) drives glioblastoma invasion. Silencing Eps8 in glioblastoma cells significantly reduced their migration and invasion, suggesting Eps8 as a potential therapeutic target.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cell Biology
Background:
- Glioblastoma multiforme (GBM) is a highly aggressive brain tumor.
- Tumor infiltration and recurrence are major challenges in GBM treatment.
- Understanding GBM invasion mechanisms is critical for developing new therapies.
Purpose of the Study:
- To investigate the role of Epidermal growth factor receptor Pathway Substrate 8 (Eps8) in glioblastoma cell migration and invasion.
- To assess Eps8 as a potential therapeutic target for GBM.
Main Methods:
- Small interfering RNAs (siRNAs) were used to silence Eps8 expression in human GBM cell lines.
- In vitro assays were performed in 2-dimensional (2-D) and 3-dimensional (3-D) models to evaluate cell migration and invasion.
- Actin-based cytoskeletal structures were analyzed.
Main Results:
- Silencing Eps8 significantly abrogated the migratory and invasive capacity of GBM cells in both 2-D and 3-D cultures.
- The inhibitory effect on invasion was observed regardless of the cell migration mode in the 3-D model.
- Impaired formation of actin-based cytoskeletal protrusive structures was noted upon Eps8 silencing.
Conclusions:
- Eps8 is a key regulator of glioblastoma cell invasion.
- Targeting Eps8 could be a promising strategy for developing novel anti-GBM drugs.
- Further research into Eps8 inhibition may lead to improved therapeutic outcomes for GBM patients.
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