The NG2 chondroitin sulfate proteoglycan: Role in malignant progression ofhuman brain tumours

The expression and function of NG2, a transmembrane chondroitin sulfate pro teoglycan was studied in human gliomas of various histological types in cul ture using immunocytochemistry and flow cytometry. NG2 was differentially e xpressed in the neoplasms, with higher expression in high compared to low-g rade gliomas. In acutely isolated cells from human biopsies, NG2 +ve and NG 2 -ve populations were morphologically distinct from each other, and NG2 +v e cells were more proliferative than NG2 -ve cells. The mitogens platelet d erived growth factor (PDGF-AA) and basic fibroblast growth factor (bFGF) ad ded in combination to serum-free medium (SFM) upregulated NG2 expression on glioblastoma multiforme cells in culture but had little effect on NG2 expr ession on the anaplastic astrocytoma cells. Furthermore, NG2 was colocalise d with the platelet derived growth factor alpha receptor (PDGF alpha R) and antibody blockade of the PDGF-alpha R ablated NG2 expression on the gliobl astoma multiforme cells, suggesting that increased NG2 expression in the pr esence of PDGF-AA is mediated via the PDGF-alpha R. Assays of migration and invasion indicate that NG2 +ve glioma cells migrated more efficiently on c ollagen IV and that NG2 -ve cells were more invasive than their NG2 +ve cou nterparts. The results indicate that NG2 may be, respectively, positively a nd negatively related to the proliferative and invasive capacity of glioma cells. Thus, expression of the NG2 proteoglycan may have major implications for malignant progression in glial neoplasms and may prove a useful target for future therapeutic regimens. (C) 1999 Published by Elsevier Science Lt d on behalf of ISDN. All rights reserved.