Journal Article FZJ-2015-06936

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The effect of neurosphere culture conditions on the cellular metabolism of glioma cells

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2015
Termedia Publ. House73588 Pozna´n [u.a.]

Folia neuropathologica 3, 219 - 225 () [10.5114/fn.2015.54422]

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Abstract: Glioblastoma (GBM) is the most common and lethal adult glial brain tumour, with a mean overall survival of 16-19 months after primary diagnosis under the current standard-of-care treatment scheme [26]. Despite enormous research efforts towards early diagnosis and more efficient treatment, the prognosis of GBMs remains dismal.The influence of culture conditions has been wi­dely investigated in the field of glioma research, suggesting that neurosphere cultures, compared to adherent growth, more closely resemble the original patient’s tumour [29] showing high stem cell compartment [1] and therefore are more suitable for testing of novel therapeutic spectras approaches [30]. In this report we describe altered relative concentrations of the cholines, creatine, myo-inositol, and glycine in the human GBM cell line U87 propagated under stem cell conditions as compared to classical monolayer culture. Furthermore, U87 neurospheres showed significant higher levels of the putative GBM stem cell marker CD133 as their serum-propagated counterparts. Detection and targeting of miss-regulated choline-, myo-inosi­tol-, creatine-, and glycine-metabolism has been de­s­cribed to have potential utility in the diagnosis and treatment of malignant gliomas [2-4,13,16,19].This is, to our knowledge, the hitherto first link of changes in those oncometabolites [4,25] to variations in cell culture conditions of glioma cells. Inter spectral co-analysis of metabolite concentrations under the two propagation conditions identified reductions in ratios of phosphocholine to glycerophosphocholine (PC/GPC) and glycine to total choline (Gly/tCho) but increases in the quotient of total choline to total creatine (tCho/tCre) and PC/tCre, as well as Gly/myo-inositol (Gly/myo). This work should draw the attention of the scientific community on possible in vitro artefacts and on the need for appropriate models most closely resembling the in vivo biology of investigated tumours.

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Contributing Institute(s):
  1. Strukturbiochemie (ICS-6)
Research Program(s):
  1. 551 - Functional Macromolecules and Complexes (POF3-551) (POF3-551)

Appears in the scientific report 2015
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Medline ; Creative Commons Attribution-NonCommercial-ShareAlike CC BY-NC-SA 4.0 ; DOAJ ; OpenAccess ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2015-11-30, last modified 2021-01-29