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

被引:25
作者
Rosi, Antonella [1 ,2 ]
Ricci-Vitiani, Lucia [3 ]
Biffoni, Mauro [3 ]
Grande, Sveva [1 ,2 ]
Luciani, Anna Maria [1 ,2 ]
Palma, Alessandra [1 ,2 ]
Runci, Daniele [3 ]
Cappellari, Marianna [3 ]
De Maria, Ruggero [4 ]
Guidoni, Laura [2 ]
Pallini, Roberto [5 ]
Viti, Vincenza [2 ]
机构
[1] Ist Super Sanita, Dept Technol & Hlth, Viale Regina Elena 299, I-00161 Rome, Italy
[2] INFN Sez Roma, Rome, Italy
[3] Ist Super Sanita, Dept Hematol Oncol & Mol Med, I-00161 Rome, Italy
[4] Regina Elena Inst Canc Res, Rome, Italy
[5] Univ Cattolica Sacro Cuore, Dept Neurosurg, Rome, Italy
关键词
glioblastoma stem-like cells; H-1 NMR spectroscopy; alpha aminoadipate; lipids; patient survival; CEREBROSPINAL-FLUID; AMINO-ACIDS; BRAIN; EXPRESSION; ASTROCYTES; UPDATE; GLIOMA; LIPIDS;
D O I
10.1002/nbm.3254
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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 H-1 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 -aminoadipate (AAD), product of the oxidation of -aminoadipic semialdehyde catalyzed by the ALDH7A1 aldehyde dehydrogenase (ALDH) family in lysine catabolism. AAD 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, AAD 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 AAD formation proceeds through saccharopine, as usually observed in developing brain. Survival curves indicated that high AAD 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. Copyright (c) 2015 John Wiley & Sons, Ltd.
引用
收藏
页码:317 / 326
页数:10
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