1H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness

Antonella Rosi, Lucia Ricci-Vitiani, Mauro Biffoni, Sveva Grande, Anna Maria Luciani, Alessandra Palma, Daniele Runci, Marianna Cappellari, Ruggero De Maria, Laura Guidoni, Roberto Pallini, Vincenza Viti

Research output: Contribution to journalArticle

Abstract

Patients suffering from glioblastoma multiforme (GBM) face a poor prognosis with median survival of about 14months. High recurrence rate and failure of conventional treatments are attributed to the presence of GBM cells with stem-like properties (GSCs). Metabolite profiles of 42 GSC lines established from the tumor tissue of adult GBM patients were screened with 1H NMR spectroscopy and compared with human neural progenitor cells from human adult olfactory bulb (OB-NPCs) and from the developing human brain (HNPCs). A first subset (n=12) of GSCs exhibited a dramatic accumulation of the metabolite α-aminoadipate (αAAD), product of the oxidation of α-aminoadipic semialdehyde catalyzed by the ALDH7A1 aldehyde dehydrogenase (ALDH) family in lysine catabolism. αAAD was low/not detectable in a second GSC subset (n=13) with the same neural metabolic profile as well as in a third GSC subset (n=17) characterized by intense lipid signals. Likewise, αAAD was not detected in the spectra of OB-NPCs or HNPCs. Inhibition of mitochondrial ATP synthase by oligomycin treatment revealed that the lysine degradative pathway leading to αAAD formation proceeds through saccharopine, as usually observed in developing brain. Survival curves indicated that high αAAD levels in GSCs significantly correlated with poor patient survival, similarly to prostate and non-small-cell-lung cancers, where activity of ALDH7A1 correlates with tumor aggressiveness.

Original languageEnglish
Pages (from-to)317-326
Number of pages10
JournalNMR in Biomedicine
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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Keywords

  • H NMR spectroscopy
  • Alpha aminoadipate
  • Glioblastoma stem-like cells
  • Lipids
  • Patient survival

ASJC Scopus subject areas

  • Spectroscopy
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

Rosi, A., Ricci-Vitiani, L., Biffoni, M., Grande, S., Luciani, A. M., Palma, A., Runci, D., Cappellari, M., De Maria, R., Guidoni, L., Pallini, R., & Viti, V. (2015). 1H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness. NMR in Biomedicine, 28(3), 317-326. https://doi.org/10.1002/nbm.3254