Culture methods of diffuse intrinsic pontine glioma cells determine response to targeted therapies

Michaël H. Meel, A. Charlotte P. Sewing, Piotr Waranecki, Dennis S. Metselaar, Laurine E. Wedekind, Jan Koster, Dannis G. van Vuurden, Gertjan J.L. Kaspers, Esther Hulleman

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Diffuse intrinsic pontine glioma (DIPG) is an aggressive type of brainstem cancer occurring mainly in children, for which there currently is no effective therapy. Current efforts to develop novel therapeutics for this tumor make use of primary cultures of DIPG cells, maintained either as adherent monolayer in serum containing medium, or as neurospheres in serum-free medium. In this manuscript, we demonstrate that the response of DIPG cells to targeted therapies in vitro is mainly determined by the culture conditions. We show that particular culture conditions induce the activation of different receptor tyrosine kinases and signal transduction pathways, as well as major changes in gene expression profiles of DIPG cells in culture. These differences correlate strongly with the observed discrepancies in response to targeted therapies of DIPG cells cultured as either adherent monolayers or neurospheres. With this research, we provide an argument for the concurrent use of both culture conditions to avoid false positive and false negative results due to the chosen method.

Original languageEnglish
Pages (from-to)397-403
Number of pages7
JournalExperimental Cell Research
Volume360
Issue number2
DOIs
Publication statusPublished - 15 Nov 2017

Cite this

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title = "Culture methods of diffuse intrinsic pontine glioma cells determine response to targeted therapies",
abstract = "Diffuse intrinsic pontine glioma (DIPG) is an aggressive type of brainstem cancer occurring mainly in children, for which there currently is no effective therapy. Current efforts to develop novel therapeutics for this tumor make use of primary cultures of DIPG cells, maintained either as adherent monolayer in serum containing medium, or as neurospheres in serum-free medium. In this manuscript, we demonstrate that the response of DIPG cells to targeted therapies in vitro is mainly determined by the culture conditions. We show that particular culture conditions induce the activation of different receptor tyrosine kinases and signal transduction pathways, as well as major changes in gene expression profiles of DIPG cells in culture. These differences correlate strongly with the observed discrepancies in response to targeted therapies of DIPG cells cultured as either adherent monolayers or neurospheres. With this research, we provide an argument for the concurrent use of both culture conditions to avoid false positive and false negative results due to the chosen method.",
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pages = "397--403",
journal = "Experimental Cell Research",
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Culture methods of diffuse intrinsic pontine glioma cells determine response to targeted therapies. / Meel, Michaël H.; Sewing, A. Charlotte P.; Waranecki, Piotr; Metselaar, Dennis S.; Wedekind, Laurine E.; Koster, Jan; van Vuurden, Dannis G.; Kaspers, Gertjan J.L.; Hulleman, Esther.

In: Experimental Cell Research, Vol. 360, No. 2, 15.11.2017, p. 397-403.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Meel, Michaël H.

AU - Sewing, A. Charlotte P.

AU - Waranecki, Piotr

AU - Metselaar, Dennis S.

AU - Wedekind, Laurine E.

AU - Koster, Jan

AU - van Vuurden, Dannis G.

AU - Kaspers, Gertjan J.L.

AU - Hulleman, Esther

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AB - Diffuse intrinsic pontine glioma (DIPG) is an aggressive type of brainstem cancer occurring mainly in children, for which there currently is no effective therapy. Current efforts to develop novel therapeutics for this tumor make use of primary cultures of DIPG cells, maintained either as adherent monolayer in serum containing medium, or as neurospheres in serum-free medium. In this manuscript, we demonstrate that the response of DIPG cells to targeted therapies in vitro is mainly determined by the culture conditions. We show that particular culture conditions induce the activation of different receptor tyrosine kinases and signal transduction pathways, as well as major changes in gene expression profiles of DIPG cells in culture. These differences correlate strongly with the observed discrepancies in response to targeted therapies of DIPG cells cultured as either adherent monolayers or neurospheres. With this research, we provide an argument for the concurrent use of both culture conditions to avoid false positive and false negative results due to the chosen method.

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