title: Novel tumor-specific isoforms of BEHAB/brevican identified in human malignant gliomas.
abstract: Malignant gliomas are deadly brain tumors characterized by diffuse invasion into the surrounding brain tissue. Understanding the mechanisms involved in glioma invasion could lead to new therapeutic strategies. We have previously shown that BEHAB/brevican, an extracellular matrix protein in the central nervous system, plays a role in the invasive ability of gliomas. The mechanisms that underlie BEHAB/brevican function are not yet understood, due in part to the existence of several isoforms that may have different functions. Here we describe for the first time the expression of BEHAB/brevican in human brain and characterize two novel glioma-specific isoforms, B/b(sia) and B/b(Deltag), which are generated by differential glycosylation and are absent from normal adult brain and other neuropathologies. B/b(sia) is an oversialylated isoform expressed by about half the high- and low-grade gliomas analyzed. B/b(Deltag) lacks most of the carbohydrates typically present on BEHAB/brevican and is the major up-regulated isoform of this protein in high-grade gliomas but is absent in a specific subset of low-grade, indolent oligodendrogliomas. B/b(Deltag) is detected on the extracellular surface, where it binds to the membrane by a mechanism distinct from the other BEHAB/brevican isoforms. The glioma-specific expression of B/b(Deltag), its restricted membrane localization, and its expression in all high-grade gliomas tested to date suggest that it may play a significant role in glioma progression and make it an important new potential therapeutic target. In addition, its absence from benign gliomas prompts its use as a diagnostic marker to distinguish primary brain tumors of similar histology but different pathologic course.
authors.affiliation: Department of Neurobiology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Mariano S
authors.initials: MS
authors.lastname: Viapiano
authors.forename: Wenya Linda
authors.initials: WL
authors.lastname: Bi
authors.forename: Joseph
authors.initials: J
authors.lastname: Piepmeier
authors.forename: Susan
authors.initials: S
authors.lastname: Hockfield
authors.forename: Russell T
authors.initials: RT
authors.lastname: Matthews
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D058581:Brevican; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D051381:Rats; D014162:Transfection
chemical_list: C546938:BCAN protein, human; D058581:Brevican; D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms