Molecular determinants of glioma cell migration and invasion.
OBJECTIVE
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.
Wild-Bode
C
C
Department of Neurology, University of Tübingen, School of Medicine, Germany.
Weller
M
M
Wick
W
W
D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; D016159:Tumor Suppressor Protein p53; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9