Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines

Please always quote using this URN: urn:nbn:de:bvb:20-opus-234110
  • Altered metabolic processes contribute to carcinogenesis by modulating proliferation, survival and differentiation. Tumours are composed of different cell populations, with cancer stem-like cells being one of the most prominent examples. This specific pool of cells is thought to be responsible for cancer growth and recurrence and plays a particularly relevant role in glioblastoma (GBM), the most lethal form of primary brain tumours. Here, we have analysed the transcriptome and metabolome of an established GBM cell line (U87) and aAltered metabolic processes contribute to carcinogenesis by modulating proliferation, survival and differentiation. Tumours are composed of different cell populations, with cancer stem-like cells being one of the most prominent examples. This specific pool of cells is thought to be responsible for cancer growth and recurrence and plays a particularly relevant role in glioblastoma (GBM), the most lethal form of primary brain tumours. Here, we have analysed the transcriptome and metabolome of an established GBM cell line (U87) and a patient-derived GBM stem-like cell line (NCH644) exposed to neurosphere or monolayer culture conditions. By integrating transcriptome and metabolome data, we identified key metabolic pathways and gene signatures that are associated with stem-like and differentiated states in GBM cells, and demonstrated that neurospheres and monolayer cells differ substantially in their metabolism and gene regulation. Furthermore, arginine biosynthesis was identified as the most significantly regulated pathway in neurospheres, although individual nodes of this pathway were distinctly regulated in the two cellular systems. Neurosphere conditions, as opposed to monolayer conditions, cause a transcriptomic and metabolic rewiring that may be crucial for the regulation of stem-like features, where arginine biosynthesis may be a key metabolic pathway. Additionally, TCGA data from GBM patients showed significant regulation of specific components of the arginine biosynthesis pathway, providing further evidence for the importance of this metabolic pathway in GBM.show moreshow less

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Author: Joana Peixoto, Sudha Janaki-Raman, Lisa Schlicker, Werner Schmitz, Susanne Walz, Alina M. Winkelkotte, Christel Herold-Mende, Paula Soares, Almut Schulze, Jorge Lima
URN:urn:nbn:de:bvb:20-opus-234110
Document Type:Journal article
Faculties:Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Cancers
ISSN:2072-6694
Year of Completion:2021
Volume:13
Issue:6
Article Number:1327
Source:Cancers (2021) 13:6, 1327. https://doi.org/10.3390/cancers13061327
DOI:https://doi.org/10.3390/cancers13061327
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:arginine metabolism; glioblastoma; metabolome; monolayer; neurospheres; transcriptome
Release Date:2022/08/26
Date of first Publication:2021/03/16
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International