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

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

13 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)317-326
Numero di pagine10
RivistaNMR in Biomedicine
Volume28
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • 1H NMR spectroscopy
  • 2-Aminoadipic Acid
  • Adult
  • Aged
  • Alpha aminoadipate
  • Biomarkers, Tumor
  • Brain Neoplasms
  • Cell Survival
  • Female
  • Glioblastoma
  • Glioblastoma stem-like cells
  • Humans
  • Kaplan-Meier Estimate
  • Lipids
  • Lysine
  • Male
  • Metabolic Networks and Pathways
  • Mitochondria
  • Molecular Medicine
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells
  • Patient survival
  • Proton Magnetic Resonance Spectroscopy
  • Radiology, Nuclear Medicine and Imaging
  • Signal Processing, Computer-Assisted
  • Spectroscopy

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