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Exp Cell Res. 2017 Nov 15;360(2):397-403. doi: 10.1016/j.yexcr.2017.09.032. Epub 2017 Sep 22.

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

Author information

1
Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: m.meel@vumc.nl.
2
Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: a.sewing@vumc.nl.
3
Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: p.waranecki@vumc.nl.
4
Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: d.metselaar@vumc.nl.
5
Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: le.wedekind@vumc.nl.
6
Department of Oncogenomics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. Electronic address: jankoster@amc.uva.nl.
7
Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: dg.vanvuurden@vumc.nl.
8
Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands. Electronic address: gjl.kaspers@vumc.nl.
9
Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: e.hulleman@vumc.nl.

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.

KEYWORDS:

Brainstem tumor; Cell culture; Kinase inhibitor; Neurosphere; Signal transduction; Targeted therapy

PMID:
28947132
DOI:
10.1016/j.yexcr.2017.09.032
[Indexed for MEDLINE]

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