CD44 MEDIATES HUMAN GLIOMA CELL-ADHESION AND INVASION IN-VITRO

Human gliomas are characterized by their invasion of normal brain stru ctures irrespective of their grade of malignancy. Factors involved in the control of this invasive behavior are poorly documented. Human gli omas have also been found to express CD44 adhesion molecules. Expressi on of splice variants of CD44 has been correlated to metastasis in non glial solid tumors. In this study, 8-mu m porosity polycarbonate filte rs incorporated in modified Boyden chambers and coated with the extrac ellular matrix composite Matrigel were used to investigate the role of CD44 in invasion of eight human glioma cell lines in vitro. Invasion of Matrigel was found to be inhibited to different extents by a CD44 m onoclonal antibody. Moreover, this invasion was highly inhibited in tw o cell lines and completely arrested in five other glioma cell lines b y a CD44-specific antisense oligonucleotide which inhibited CD44 expre ssion. In addition, adhesion of glioma cells to fibronectin, laminin, vitronectin, and collagen I was inhibited by the CD44 monoclonal antib ody. These results strongly suggest that CD44 is involved in human gli oma cell invasion in vitro, probably through its role in cell interact ions with extracellular matrix proteins. Interference with glioma inva sion, by targeting CD44 expression, may be envisaged in animal models.