Gliomas are the most common primary intracranial
tumors. One extracellular matrix component that has been implicated in glial
tumor biology is brain enriched
hyaluronan binding (BEHAB)/
brevican. In this study, the CNS-1 rat
glioma cell line was transfected with a vector containing either a full-length BEHAB/
brevican cDNA, a 5' insert encoding the NH(2)-terminal BEHAB/
brevican cleavage product, or a 3' insert encoding the COOH-terminal cleavage product. As a control, CNS-1 cells were transfected with
green fluorescent protein. Rats with intracranial grafts of BEHAB/
brevican-transfected CNS-1 cells displayed significantly shorter survival times than did rats with CNS-
green fluorescent protein intracranial grafts (P < 0.001). Histological examination showed that the BEHAB/
brevican-transfected
tumors were just as, if not more, aggressive than control
tumors, even though the BEHAB/
brevican tumors had been growing for only approximately two-thirds the time as long as control
tumors. These data suggest that up-regulation and proteolytic cleavage of BEHAB/
brevican increase significantly the aggressiveness of glial
tumors. It will be important to investigate the effect of inhibiting cleavage of BEHAB/
brevican in these cells and to determine the therapeutic potential of inhibiting BEHAB/
brevican cleavage in
gliomas.