¹H 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.

Differential expression of novel metabolic and immunological biomarkers in oysters challenged with a virulent strain of OsHV-1

“…Accumulations of 2-AAA are also associated with oncogene activation and carcinogenesis, leading to its recent candidacy as a potential new clinical biomarker for various cancers (Hori et al 2011;Bellance et al 2012;Jung et al 2013;Rosi et al 2015;Ren et al 2016).…”

Applications of high‐resolution magic angle spinning MRS in biomedical studies I—cell line and animal models

“…MRS has been widely used as an analytical method in biochemical and biomedical studies to elucidate molecular structures of new compounds and investigate cellular metabolism in tissue specimens and cultured cells . MRS has further found broad implementation in investigations of new diagnostic, prognostic and therapeutic evaluation tools for a wide range of diseases …”

“…MRS has been widely used as an analytical method in biochemical and biomedical studies to elucidate molecular structures of new compounds 1,2 and investigate cellular metabolism in tissue specimens 3 and cultured cells. 4 MRS has further found broad implementation in investigations of new diagnostic, prognostic and therapeutic evaluation tools for a wide range of diseases. [5][6][7][8] Metabolites are the signatures of biochemical pathways, providing insight into cellular carbohydrate, protein, lipid, amino acid and xenobiotic metabolism.…”

Metabolomic signature of brain cancer

“…For example, the elevation of hexosamine pathway metabolic intermediates in brain cancer cell lines (rat GBM, human GBM, human supratentorial primitive neuroectodermal tumor (ST‐PNET), and human medulloblastoma) are linked to cancer cell death following cisplatin treatment . NMR analysis of GBM stem cells identified a high level of α‐aminoadipate (αAAD) in GBM as a marker of tumor aggressiveness …”

“…184 NMR analysis of GBM stem cells identified a high level of α-aminoadipate (αAAD) in GBM as a marker of tumor aggressiveness. 186 Despite the limited number of primary samples compared to the in vitro experiments, several labs have analyzed brain biopsies, plasma/serum, urine, and CSF samples from astrocytoma and GBM patients. Most of these studies were able to identify distinct metabolic patterns associated with diagnosis and prognosis of brain cancer patients (Table 1).…”