Characteristic metabolic profiles revealed by ¹H NMR spectroscopy for three types of human brain and nervous system tumours

Abstract

Cell culture techniques, high-resolution in vitro 1H NMR spectroscopy, and chromatographic analyses were used to compare the properties of three types of human brain and nervous system tumours. Cell lines were immunocytochemically characterized at all stages in culture with specific antibodies. Intracellular metabolites present in cell extracts were analysed by 1H NMR spectroscopy and by high performance liquid chromatography (HPLC). The spectra from meningiomas, neuroblastomas, and glioblastomas displayed, in addition to similarities-including the presence of signals from leucine, isoleucine, valine, threonine, lactate, acetate, glutamate, choline-containing compounds and glycine-certain distinguishing metabolic features. Spectra from meningiomas featured relatively high signals from alanine. Intense signals from creatine were present in neuroblastoma spectra, while in spectra from glioblastoma they were not detectable. We found statistically significant differences by 1H NMR spectroscopy in the amounts of alanine, glutamate, creatine, phosphorylcholine and threonine among the types of tumours examined. HPLC determinations confirmed that there were also other metabolites specific to a type of tumour, such as taurine, gamma-aminobutyric acid, and serine. We suggest that these findings have potential relevance for the development of non-invasive diagnosis of tumour lineage by 1H NMR spectroscopy in vivo.

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

“…This was in contrast to the relatively tight distribution of the corresponding metabolites (variation up to a factor of 5) reported by Florian et al (1996) in different cell lines comprising well-differentiated brain and nervous system tumours (either neuroblastomas, glioblastomas or meningiomas). An explanation for this may reside in the several degrees and directions of commitment in differentiation towards various lineages of the CNS of the medulloblastoma cells examined here.…”

“…There is a possibility that the expression of NAA by medulloblastomas reflects, in fact, their origin from a progenitor cell with the phenotypic characteristics of an 0-2A progenitor cell, rather than of a neuronal progenitor. Nonetheless, the highly significant differences in NAA levels between cerebellar medulloblastomas and PNETs from other CNS locations may suggest differences in lineage origin for these tumours, as well as differences from other tumours of the CNS, which have been studied by Florian et al (1995Florian et al ( , 1996.…”

Noninvasive estimation of tumour viability in a xenograft model of human neuroblastoma with proton magnetic resonance spectroscopy (1H MRS)

“…Intense creatine and Cho signals were found in 1 H MRS spectra from perchloric extracts of neuroblastoma cells. (Florian et al, 1995). When neuroblastoma cells were implanted in rat brain, a prominent Cho peak but no creatine was detected in vivo with 1 H MRS (Gyngell et al, 1994).…”

Proton MR spectroscopy in clinical routine

“…Starting with the interpretation of metabolite ratios and quantitative MRS data acquired by means of single-volume spectroscopy measurements covering large and heterogeneous parts of the lesions, several spectral characteristics could be associated to different tumor groups, although large overlaps, questioning the specificity, were observed (8,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). Consistent findings were the decrease and ultimately loss of NAA resonances in tumors derived from other-than-neuronal tissue and an increase in choline-containing compounds representing increased cell turnover, cell density, and gliosis (Fig.…”