CD24 promotes invasion of glioma cells in vivo

Based on the hypothesis that adhesion molecules expressed on the surface of glioma cells mediate brain invasion, we examined the effect of CD24 on gro wth and migration of gliomas in vitro and in vivo. CD24, a glycosylphosphat idyl inositol anchored, highly glycosylated adhesion molecule, is expressed in hematopoietic and neural cells. We found immunohistochemical expression of CD24 in human,glioblastomas. We then established a clone from C6 rat gl ioblastoma cells, where mouse CD24 (also called heat stable antigen) is und er control of a tetracycline-responsive promoter. In the presence of tetrac ycline (1 mu g/ml) CD24 was downregulated by 20-fold. In vitro migration as says were performed on a basement membrane preparation (matrigel) and on my elin, the main substrates of in vivo glioma migration. While the cells were more motile on matrigel as compared with myelin, no relation between CD24 expression and motility was observed. We then transplanted the C6 clone int o the striatum of nude mice and regulated CD24 expression via tetracycline in the drinking water (1 mg/ml). After 3 weeks, CD24 positive tumors of mic e getting no tetracycline showed diffuse invasion of tumor cells in a brain area 10-fold larger than in CD24-suppressed tumors of mice receiving tetra cycline. These data show that CD24 stimulates migration of gliomas in vivo and they suggest a role for this adhesion molecule in diffuse brain invasio n of human gliomas.