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Biomedical subjects

D Davies

Publications and source records attributed to D Davies.

At least 235 records · Page 13Linked to original sources

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.

Brain Neoplasms↗

The role of integrin receptors in aspects of glioma invasion in vitro.

Integrins are heterodimers consisting of non-covalently associated alpha and beta subunits. They mediate adherence of normal and tumour cells to the extracellular matrix, a property which is essential for migration of neoplastic astrocytes as they invade into the normal brain parenchyma. Flow cytometry and immunocytochemical analysis of cultured cells derived from 10 gliomas (1 pilocytic astrocytoma, 1 astrocytoma, 1 oligoastrocytoma, 1 anaplastic oligoastrocytoma, 4 anaplastic astrocytomas and 2 glioblastoma multiforme) revealed that the beta1 integrin subunit was generally expressed more strongly than alpha4 or alpha(v) integrin subunits. Subsequent studies with function-blocking antibodies against the beta1 subunit inhibited adhesion, motility and invasion of the gliomas in vitro, to varying degrees, on all extracellular matrix substrates investigated (laminin, collagen type IV, fibronectin and vitronectin), the inhibition by beta1 subunit was greatest on collagen type IV. These studies therefore substantiate the case for a role of the beta1 integrin subunit in neoplastic glial cell invasion of the brain.

Brain Neoplasms↗

Embryo research.

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Embryo, Mammalian↗