Glial Tumor Invasion: A Role for the Upregulation and Cleavage of BEHAB/Brevican

Abstract

Glial tumors, gliomas, are the most common primary intracranial tumors. Their distinct ability to invade the normal surrounding tissue makes them difficult to control and nearly impossible to completely remove surgically, and it accounts for the extraordinarily high lethality associated with gliomas. The ability of these transformed glial cells to invade the normal surrounding tissue is relatively unique in the adult CNS, which under most circumstances, is inhibitory to cell movement. The extracellular matrix (ECM) can modulate, in part, the permissiveness of a tissue to cell movement. Accordingly, the ability of gliomas to modify the ECM of the CNS may mediate the invasiveness of these cells. One ECM molecule that shows dramatic upregulation in gliomas is BEHAB (brain enriched hyaluronan binding)/brevican, a brain-specific chondroitin sulfate proteoglycan. BEHAB/brevican expression is also upregulated during periods of increased glial cell motility in development and following brain injury. Experimental evidence suggests that in glioma, in addition to upregulation of BEHAB/brevican, proteolytic processing of the full-length protein also may contribute to invasion. Here, the authors present a review of the literature on glial tumor invasion by modulation of the ECM and propose a two-step model for BEHAB/brevican’s role in this process.