The expression and function of NG2, a transmembrane
chondroitin sulfate proteoglycan was studied in human
gliomas of various histological types in culture using immunocytochemistry and flow cytometry. NG2 was differentially expressed in the
neoplasms, with higher expression in high compared to low-grade
gliomas. In acutely isolated cells from human biopsies, NG2 +ve and NG2 -ve populations were morphologically distinct from each other, and NG2 +ve cells were more proliferative than NG2 -ve cells. The
mitogens platelet derived growth factor (
PDGF-AA) and
basic fibroblast growth factor (bFGF) added in combination to serum-free medium (SFM) upregulated NG2 expression on
glioblastoma multiforme cells in culture but had little effect on NG2 expression on the
anaplastic astrocytoma cells. Furthermore, NG2 was colocalised with the
platelet derived growth factor alpha receptor (PDGFalphaR) and antibody blockade of the PDGF-alphaR ablated NG2 expression on the
glioblastoma multiforme cells, suggesting that increased NG2 expression in the presence of
PDGF-AA is mediated via the PDGF-alphaR. Assays of migration and invasion indicate that NG2 +ve
glioma cells migrated more efficiently on
collagen IV and that NG2 -ve cells were more invasive than their NG2 +ve counterparts. The results indicate that NG2 may be, respectively, positively and 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.