Gliomas are the most common and lethal primary tumors of the CNS. The invasive nature of these tumors make them difficult to treat and nearly impossible to completely surgically resect. One major barrier to invasion in all tissues, including the brain, is the extracellular matrix (ECM). Gliomas, in contrast to most other intracranial neoplasms, are able to overcome this barrier through a variety of mechanisms, including proteolytic cleavage of and modified interactions with the ECM. One molecule implicated in modification of the ECM by infiltrative glia is the brain-enriched hyaluronan-binding protein (BEHAB)/brevican. BEHAB/brevican mRNA levels are upregulated during periods of glial proliferation and motility, such as during the peak of gliogenesis and during reactive gliosis. BEHAB/brevican message is also dramatically upregulated in gliomas. We describe here a novel protein isoform of BEHAB/brevican, B/bΔg, that is absent from normal adult brain but is specifically and highly expressed in high-grade gliomas. B/bΔg runs in SDS-PAGE at a lower molecular weight than normal full-length BEHAB/brevican. However, B/bΔg is not a cleavage product or splice variant of full-length BEHAB/brevican. Instead, B/bΔg is an underglycosylated variant that lacks most of the carbohydrates typically found on BEHAB/brevican. Despite this, B/bΔg does not represent an unprocessed form of the protein that is sequestered inside the cell. Rather, B/bΔg is secreted to and found exclusively in association with the cell membrane, unlike other isoforms of BEHAB/brevican. The exclusive expression and cell-surface localization of B/bΔg in glioma makes this molecule a potential diagnostic and therapeutic target in these tumors.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]