NG2 and its relationship to Adult and Childhood Brain Tumours (Dr. A. Butt)
3 year project with a grant of £73,775.00
1998 - 2001
NG2 is a member of a group of molecules that “stick out” from the surface of cells and help them interact within the external environment, which is important in the malignancy and invasiveness of brain tumours. The project has shown novel and exciting results demonstrating that NG2 identifies some cells in paediatric brain tumours and has provided the first evidence that NGS is involved in brain tumour cell proliferation and may help facilitate brain tumour cell invasion through the brain.
NG is a transmembrane chondroitin sulfate proteoglycan (CSPG), which is expressed by glial restricted stem cells in the mammalian and human central nervous system (CNS). These cells retain the ability to differentiate into glia in the mature brain and, we suggest, may give rise to gliomas. We proposed the immunolabelling with antibodies to NG2 will be a useful means of identifying different grades of gliomas and may provide some indication of their cellular origin. In addition, the functions of the NG2 molecule in mediating cell-cell and cell-extracellular matrix interactions raised the possibility that NG2 may be important in the growth and migration of neoplastic cells. It was our hypothesis, therefore, that NG2 expression may be related to gliomas growth and invasiveness. The aim of the project was to determine the expression and function of NG2 in human gliomas of various histological types in tissue sections, in culture, and in experimental animal models. Conclusion:
In conclusion, three major findings of the project were: (1) NG2 is expressed by most gliomas, with highest expression in high grade gliomas; (2) NG2 expression is positively correlated with cellular proliferation, but was inversely related to tumour cell invasion; (3) NG2 regulates the transition from small, poorly vascularized gliomas to large and highly vascular gliomas in situ by sequestering angiostatin. These findings have important diagnostic and therapeutic implications. They suggest that most gliomas have a common cellular source, namely resident glial stem cells, which are a significant population of cells in the developing and adult brain. Since the NG2 molecule plays a role in gliomas growth and angiogenesis, the future studies should focus both on the molecular and cellular mechanisms of NG2 function and on the possibility of targeting NG2 in gliomas cells, using both genetic and pharmacological tools.
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