PXD024019

PXD024019 is an original dataset announced via ProteomeXchange.

Title	Effects of the IDH1 R132H mutation on the energy metabolism: a comparison between tissue and corresponding primary glioma cell cultures
Description	The R132H mutation in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) is the most important prognostic factor for survival of glioma patients. This resulted in many studies investigating the effects of this mutation, including those on energy metabolism. This led to the discovery of a panel of enzymes mainly involved in glutamate anaplerosis and aerobic glycolysis that change in abundance as a result of the IDH1 mutation. To further study these changes and investigate the therapeutic value of inhibitors of IDH1 R132H-associated metabolic pathways, appropriate glioma models are required that mimic in vivo metabolism as good as possible. To investigate how metabolism is affected by in vitro cell culture, we here compared surgically obtained snap frozen glioma tissues with their corresponding primary glioma cell culture models with a previously developed targeted mass spectrometry proteomic assay. We determined the relative abundance of a panel of metabolic enzymes. Results confirmed increased glutamate use and decreased aerobic glycolysis in resected IDH1 R132H glioma tissue samples. However, these metabolic profiles were not reflected in the paired glioma culture samples. Analysis of orthotopic glioma xenograft samples with and without the IDH1 mutation revealed metabolic profiles that more closely resembled clinical counterparts. We suggest that culture conditions and tumor microenvironment play a crucial role in maintaining the in vivo metabolic situation in cell culture models. For this reason, new models that more closely resemble the in vivo microenvironment, such as 3-dimensional cell co-cultures or organotypic multicellular spheroid models, need to be developed and investigated.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_14:22:26.573.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lennard Dekker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-05 03:16:47	ID requested
⏵ 1	2022-02-16 14:22:27	announced

Dekker LJM, Verheul C, Wensveen N, Leenders W, Lamfers MLM, Leenstra S, Luider TM, Effects of the IDH1 R132H Mutation on the Energy Metabolism: A Comparison between Tissue and Corresponding Primary Glioma Cell Cultures. ACS Omega, 7(4):3568-3578(2022) [pubmed]

submitter keyword: Glioma, IDH1 R132H mutation, Cell cultures, Proteomics, Energy metabolism

Theo Luider
contact affiliation	Erasmus MC Department of Neurology Laboratory of Neuro-oncolgy
contact email	t.luider@erasmusmc.nl
lab head
Lennard Dekker
contact affiliation	Erasmus MC
contact email	l.dekker@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024019
     1. Label: PRIDE project
     2. Name: Effects of the IDH1 R132H mutation on the energy metabolism: a comparison between tissue and corresponding primary glioma cell cultures