posted on 2022-01-20, 00:43authored byLennard
J. M. Dekker, Cassandra Verheul, Nicky Wensveen, William Leenders, Martine L. M. Lamfers, Sieger Leenstra, Theo M. Luider
The R132H mutation
in the metabolic enzyme isocitrate dehydrogenase
1 (IDH1) is the most important prognostic factor for the survival
of glioma patients. Subsequent studies 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, appropriate glioma models are required
that accurately mimic in vivo metabolism. 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 primary cell cultures. 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 three-dimensional cell co-cultures or organotypic multicellular
spheroid models, need to be developed and investigated.