Suppression of CD44 expression decreases migration and invasion of human glioma cells

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-251AI. The expression of CD44H in the G-418-selected U-251AI cells was reduced to 20% of that in the parental U-251SP cells, as determined by now-cytometry analysis. We first examined the migratory responses of U-251AI cells in vitro by time-lapse video-microscopic sparse cell-migration assay on hyaluronic acid or on chondroitin 6 sulfate. U-251AI cells did not show significant differences in motility on any substrate, while U-251SP and other CD44H-positive glioma cells showed dose-dependent increase of migration specifically on hyaluronic acid. To examine the physiologic function of CD44H in gliomas in vivo, U-251AI and its control cells, U-251SI, which retain CD44-sense-expression vector, were injected stereotactically into the brains of nude mice. U-251AI 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. (C) 1996 Wiley-Liss, Inc.