BEHAB/brevican requires ADAMTS-mediated proteolytic cleavage to promote glioma invasion

摘要: Malignant gliomas are the most common and deadly primary brain tumors, due to their infiltrative invasion of normal neural tissue that makes them virtually impossible completely eliminate. We have previously identified characterized proteoglycan BEHAB/brevican in demonstrated upregulation cleavage this CNS-specific molecule promote glioma invasion. Here, we further investigated if proteolytic processing by metalloproteases ADAMTS family is a necessary step mediating its pro-invasive effect glioma. By generating site-specific (396SRG398 → NVY) mutant form resistant cleavage, shown predominant cells occurs only at site. More importantly, “uncleavable” unable enhance cell vitro tumor progression vivo. In addition, our results suggest full-length protein products may act independently because does not exert dominant negative on expression or cleavage. These illustrate how regulated major components extracellular matrix has important functional implications progression. findings underscore relevance as attractive targets for novel pharmacological approaches therapy.