EFFECT OF CHANGES IN THE CD44 GENE ON TUMOR-CELL INVASION IN GLIOMAS

Cell adhesion is a critical factor in the multistep process of tumour invasion. CD44 is one of the cell surface adhesion molecules responsib le for interaction with hyaluronic acid, a component of the CNS extrac ellular matrix. The aim of the present study was to demonstrate whethe r alterations in the CD44 gene might account for different invasive be haviour. EcoRI restriction analysis by Southern blot hybridization rev ealed several additional hybridization signals in tissue specimens of two out of 16 patients with glioblastoma, indicating DNA rearrangement s or point mutations, respectively, within the region of the CD44 gene . Expression patterns of CD44 isoforms in these two rearranged gliomas and in 28 other patients with malignant gliomas were analysed by RT-P CR. All cases displayed only the splice variant CD44H, which acts as h yaluronic acid receptor in glioma tumour cells. Tumour cell invasion w as studied with Boyden chamber assays using hyaluronic acid as ligand and functional CD44H blocking antibody. Invasion of cells derived from those gliomas carrying the rearranged CD44 gene locus was decreased b y about 50% compared with gliomas without rearrangement, indicating th at the altered hybridization patterns in the two glioma samples influe nced CD44H mediated glioma cell invasion through hyaluronic acid in vi tro. Our results on CD44 isoform expression suggest that, in contrast to other solid tumours, gliomas seem to express only the CD44 variant. Genetic alterations within the CD44 gene might alter the binding doma in of the receptor and thus account for different invasive behaviour i n glioblastomas.