Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of CNS-1 gliomas in Lewis rats

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.