The NG2 chondroitin sulfate proteoglycan: role in malignant progression of human brain tumours.
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.
Chekenya
M
M
Experimental Neuro-oncology Group, Department of Neuropathology, Institute of Psychiatry, King's College, London, UK.
Rooprai
H K
HK
Davies
D
D
Levine
J M
JM
Butt
A M
AM
Pilkington
G J
GJ
D001932:Brain Neoplasms / Q000737:chemistry / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis / Q000502:physiology*; D018450:Disease Progression; D005434:Flow Cytometry; D005910:Glioma / Q000737:chemistry / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D014407:Tumor Cells, Cultured
D011508:Chondroitin Sulfate Proteoglycans; D017479:Receptors, Platelet-Derived Growth Factor