title: (1) H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness.
abstract: Patients suffering from glioblastoma multiforme (GBM) face a poor prognosis with median survival of about 14 months. 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 (1) H 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.
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy; INFN Sezione di Roma, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Rosi
authors.forename: Lucia
authors.initials: L
authors.lastname: Ricci-Vitiani
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffoni
authors.forename: Sveva
authors.initials: S
authors.lastname: Grande
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Luciani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Palma
authors.forename: Daniele
authors.initials: D
authors.lastname: Runci
authors.forename: Marianna
authors.initials: M
authors.lastname: Cappellari
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
authors.forename: Laura
authors.initials: L
authors.lastname: Guidoni
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
authors.forename: Vincenza
authors.initials: V
authors.lastname: Viti
mesh_terms: D015074:2-Aminoadipic Acid / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D066244:Proton Magnetic Resonance Spectroscopy; D012815:Signal Processing, Computer-Assisted
chemical_list: D014408:Biomarkers, Tumor; D015074:2-Aminoadipic Acid; D008239:Lysine; C100169:saccharopine
keywords: 1H NMR spectroscopy; alpha aminoadipate; glioblastoma stem-like cells; lipids; patient survival