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Suppression of CD44 expression decreases migration and invasion of human glioma cells
1Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
Abstract:
We have reported high expression of CD44H in human glioma cells. To investigate the role of CD44H in the invasion of human glioma, we established a CD44-anti-sense-gene-expression glioma cell line named U-251A1. The expression of CD44H in the G-418-selected U-251A1 cells was reduced to 20% of that in the parental U-251SP cells, as determined by flow-cytometry analysis. We first examined the migratory responses of U-251A1 cells in vitro by time-lapse video-microscopic sparse cell-migration assay on hyaluronic acid or on chondroitin 6 sulfate. U-251A1 cells did not show significant differences in motility on any substrate, while U-251SP and other CD44H-positive cells showed dose-dependent increase of migration specifically on hyaluronic acid. To examine the physiologic function of CD44H in gliomas in vivo, U-251A1 and its control cells, U-251S1, which retain CD44-sense-expression vector, were injected stereotactically into the brains of nude mice. U-251A1 cells were localised in the region of the injection site, with relatively well demarcated borders between tumour and brain tissue, while the control cells demonstrated a cell-infiltration pattern. Our data suggest that CD44H may be required for infiltration of glioma cells through its interaction with hyaluronic acid, a major component of the brain extracellular matrix.
Insights
High expression of CD44H in glioma cells was investigated. Reduced CD44H expression inhibited glioma cell infiltration in vivo, suggesting CD44H is crucial for glioma invasion via hyaluronic acid interaction.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cell Biology
Background:
- High expression of CD44H (a cell surface glycoprotein) is observed in human glioma cells.
- CD44H is implicated in various cellular processes, including cell adhesion, migration, and invasion.
- Understanding the role of CD44H in glioma invasion is critical for developing targeted therapies.
Purpose of the Study:
- To investigate the specific role of CD44H in the invasion of human glioma cells.
- To determine if CD44H mediates glioma cell migration and infiltration through interactions with extracellular matrix components.
Main Methods:
- Establishment of a CD44-anti-sense-gene-expression glioma cell line (U-251A1) with reduced CD44H expression.
- In vitro cell migration assays using time-lapse video-microscopy on hyaluronic acid and chondroitin 6 sulfate.
- In vivo stereotactic injection of U-251A1 and control cells into the brains of nude mice to assess tumor invasion patterns.
Main Results:
- U-251A1 cells exhibited significantly reduced CD44H expression (20% of parental cells).
- In vitro, U-251A1 cells showed no significant difference in motility, while CD44H-positive cells demonstrated dose-dependent migration on hyaluronic acid.
- In vivo, U-251A1 cells formed localized tumors with demarcated borders, whereas control cells displayed invasive infiltration patterns.
Conclusions:
- CD44H expression is essential for the invasive potential of human glioma cells.
- CD44H likely mediates glioma cell infiltration through its interaction with hyaluronic acid, a key component of the brain extracellular matrix.
- Targeting the CD44H-hyaluronic acid interaction may represent a therapeutic strategy to inhibit glioma invasion.