Metabolic studies of human primitive neuroectodermal tumour cells by proton nuclear magnetic resonance spectroscopy

Abstract

Summary Well-characterized cell lines established from primitive neuroectodermal tumours (PNETs) were examined by proton nuclear magnetic resonance ('H-NMR) spectroscopy and chromatographic analysis of perchloric acid extracts, following amplification in cell culture. A characteristic 'H-NMR spectroscopic metabolite pattern was found for medulloblastoma cell lines, which clearly discriminates these cells from PNETs of other locations in the central nervous system (CNS), on the basis of their N-acetyl aspartate (NM) and aspartate expression. Medulloblastoma cell lines were heterogeneous in respect of their metabolite expression, possibly owing to the heterogeneity in their differentiation along lineages of the CNS. All PNET spectra displayed similar features, including decreased NAA and creatine peaks and increased signals from choline compounds (Cho) compared with normal cerebellum. The expression of NM by the medulloblastoma lines was in the opposite order to the extent of neuronal differentiation, which may indicate their origin from a progenitor cell with the phenotype of an oligodendrocyte-type-2 astrocyte cell.Keywords: human primitive neuroectodermal tumour; human medulloblastoma; proton nuclear magnetic resonance spectroscopy; metabolite; cell line Primitive neuroectodermal tumours (PNETs) are highly malignant [grade IV according to the World Health Organization classification of brain tumours by Kleihues et al (1993)] and among the most common tumours of childhood. They are most frequently located in the cerebellum (i.e. cerebellar medulloblastomas), but tumours that have a similar appearance and biological behaviour have been found in other locations in the central nervous system (CNS), such as the cerebrum, pineal region or spinal cord. The nature and cell of origin of these tumours, composed of primitive or undifferentiated neuroepithelial cells, is controversial. Questions have been raised as to whether their cell of origin is unique to the portion of the CNS in which the tumour arises, or whether there is a primitive or undifferentiated cell common to all portions of the CNS. Rorke et al (1985) have suggested that these tumours arise from a single primitive multipotential cell that has the capacity to differentiate into one or more types of neural cellssuch as astrocytes, oligodendrocytes, neurons, ganglion cells or melanocytes -and are therefore regarded as malignant counterparts of multipotential neural progenitor cells.Progress in understanding the cell biology of these tumours has been hampered by the lack of cultured cell lines, since relatively few continuous medulloblastoma lines have been established thus far (Friedman et al, 1985;Jacobsen et al, 1985). However, the recent establishment of five new human PNET cell lines from surgical specimens (Pietsch et al, 1994) Correspondence to: S Williams investigate the biology, phenotype, lineage and metabolism of PNETs in detail. In the present study, metabolite profiles of several of these PNET cell lines in culture, together with two establishe...

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