Oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells transformed with c-myc and H-ras form high-grade glioma after stereotactic injection into the rat brain

Abstract

The oligodendrocyte-type-2 astrocyte lineage (O-2A) comprises a progenitor cell that is able to differentiate into an oligodendrocyte or astrocyte in vitro. The lineage was originally identified in the neonatal rat central nervous system but evidence suggests that the equivalent O-2A lineage also exists in humans. Apart from its putative and widely studied role in glial repair, this cell type could potentially be involved in malignant glioma formation. In this study we demonstrate that a rat O-2A progenitor cell line carrying the bacterial β-galactosidase reporter gene and transformed with the c-myc and H-ras oncogenes which has lost its differentiation capacity in vitro generates glioma-like growth after stereotactic injection into the adult rat brain. Tumour pathology was similar to human glioblastoma, suggesting that one of the pathways in the generation of human glioblastomas may be the transformation of adult O-2A progenitor cells. Parallel studies demonstrated the presence of a DNA-binding protein complex, termed APprog, in a panel of human glioma cell lines. This protein was initially identified in O-2A progenitor cells and not their differentiated progeny. These data lead us to propose that APprog could be used as an indicator of the lineage origin of gliomas.