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Molecular determinants of glioma cell migration and invasion
C Wild-Bode1, M Weller, W Wick
1Department of Neurology, University of Tübingen, School of Medicine, Germany.
Object:
Migration and invasion are important prerequisites for the infiltrative and destructive growth patterns of malignant gliomas. Infiltrative growth prevents complete tumor resection and causes significant neurological morbidity and mortality.
Methods:
The authors assessed the expression of matrix metalloproteinases (MMPs) at messenger RNA and protein levels, MMP-2 and MMP-9 activities, and expression levels of a panel of anti- and proapoptotic proteins of the BCL-2 family. They then correlated their findings with alpha(v)beta3 integrin expression and the migratory and invasive potentials in 12 human malignant glioma cell lines. Multiple MMPs were expressed by most cell lines. The levels of MMP-2 and MMP-3 and the activities of MMP-2 and MMP-9 correlated with tumor cell invasion. Migration and invasion were also correlated. Although the expression levels of alpha(v)beta3 integrin did not predict migration or invasion, a neutralizing alpha(v)beta3 integrin antibody inhibited migration and invasion selectively in cell lines that contained a high level of alpha(v)beta3 integrin expression, thus indicating the important role of alpha(v)beta3 integrin for migration and invasion in this subset of cell lines. An expression pattern of BCL-2 family proteins that favor resistance to apoptosis was associated with enhanced migration, invasion, and MMP activity. Wild-type p53 cell lines migrated farther than mutant p53 cell lines.
Conclusions:
Activities of MMP-2 and MMP-9 are the best predictors of glioma cell invasion. The alpha(v)beta3 integrin mediates migration and invasion in a subset of glioma cell lines, but these processes do not depend on alpha(v)beta3 integrin expression. Antiapoptotic BCL-2 family protein expression is a predictor of efficient migration and invasion.
Insights
Matrix metalloproteinase (MMP) activities predict glioma cell invasion. Alpha(v)beta3 integrin mediates migration in some gliomas, while antiapoptotic BCL-2 proteins enhance invasion and migration.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Cellular Motility
Background:
- Malignant gliomas exhibit infiltrative growth, hindering resection and causing significant morbidity.
- Understanding glioma cell migration and invasion is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the predictors of malignant glioma cell migration and invasion.
- To assess the roles of matrix metalloproteinases (MMPs), alpha(v)beta3 integrin, and BCL-2 family proteins in glioma cell motility.
Main Methods:
- Assessed MMP expression (mRNA, protein, activity) and BCL-2 family protein levels in 12 human malignant glioma cell lines.
- Correlated these factors with alpha(v)beta3 integrin expression and cell migration/invasion potentials.
- Utilized a neutralizing alpha(v)beta3 integrin antibody to evaluate its effect on migration and invasion.
Main Results:
- MMP-2 and MMP-9 activities were the strongest predictors of glioma cell invasion.
- Alpha(v)beta3 integrin mediated migration and invasion in a subset of cell lines, but not all.
- Expression of antiapoptotic BCL-2 family proteins correlated with enhanced migration, invasion, and MMP activity.
- Wild-type p53 glioma cells showed greater migration than mutant p53 cells.
Conclusions:
- MMP-2 and MMP-9 activities are key indicators of glioma invasiveness.
- Alpha(v)beta3 integrin plays a role in migration and invasion in specific glioma contexts.
- Antiapoptotic BCL-2 proteins are associated with increased glioma cell migration and invasion.