DIFFERENTIAL EXPRESSION OF VERSICAN ISOFORMS IN BRAIN-TUMORS

Versican is a member of the family of large aggregating chondroitin su lfate proteoglycans which are one of the major constituents of brain e xtracellular matrix (ECM). We examined the expression of versican spli ce variants at mRNA and protein levels in normal human brain and in gl iomas, medulloblastomas, schwannomas, neurofibromas, and meningiomas. RT-PCR revealed transcripts for V0 and V1 in all tissues. V2 mRNA was restricted to gliomas and normal brain, while V3 mRNA was detected in all tissues except for medulloblastomas. Immunohistochemistry using an tibodies to the glycosaminoglycan (GAG)-alpha attachment domain of ver sican (present in V0 and V2) revealed decreased staining of most gliom a ECMs compared to normal neuropil, while some abnormal tumor vessels, but not normal cerebral vessels, were GAG-alpha-positive. Expression of the GAG-beta attachment domain (present in V0 and V1) was faint in normal neuropil and cerebral vessels, but increased in tumor vessels a nd was absent in most glioma ECMs. Both GAG-alpha and GAG-beta were ex pressed in connective tissue of all nonglial tumors. Our data suggest that V2 is the major versican isoform of normal neuropil and glioma EC M. Furthermore, increased expression in tumor vessels and decreased ex pression in glioma ECM of the anti-adhesive versican may be related to marked local invasivity and rarity of extracranial metastasis of glio mas.