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Updated: Jun 10, 2026

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib mesylate
Ingo Neumann1, Jürgen L Foell, Marianne Bremer
1Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Background:
Retinoids can induce differentiation of neuroblastoma (NB) cells and are in clinical use for the treatment of patients with NB. Despite improvements of standard treatment during the last years, many patients with NB still relapse and new treatment options for these patients are required.
Procedure:
We analyzed NB cells after incubation with retinoids by using Affymetrix HG_U133A microarrays, reverse transcription-polymerase chain reaction (RT-PCR), and flow cytometry. Sequencing of RT-PCR products was applied for determination of CD117 mRNA sequences from NB cell lines. In addition, we tested sensitivity of NB cells for the kinase inhibitor imatinib mesylate after treatment with retinoids.
Results:
Treatment of NB cells with retinoids induced expression of several genes including the retinoid metabolizing enzymes CYP26A1 and CYP26B1. In addition, we observed up-regulation of CD117 (KIT), particularly after long-term treatment with retinoids. Sequencing of CD117 mRNA from NB cell lines revealed heterozygosity for a non-synonymous single nucleotide polymorphism in SH-SY5Y NB cells. Up-regulation of CD117 in NB cells correlated with increased sensitivity for the kinase inhibitor imatinib mesylate.
Conclusions:
The combination of retinoids with kinase inhibitors might be worth exploring further for the treatment of NB patients.
Insights
Retinoids increase CD117 (KIT) expression in neuroblastoma (NB) cells, enhancing their sensitivity to kinase inhibitors like imatinib mesylate. This suggests a potential new combination therapy for relapsed NB patients.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Retinoids are used to treat neuroblastoma (NB), but relapses necessitate new therapeutic strategies.
- Understanding retinoid effects on NB cells is crucial for improving treatment outcomes.
Purpose of the Study:
- To investigate the molecular effects of retinoid treatment on neuroblastoma cells.
- To explore potential combination therapies for neuroblastoma.
Main Methods:
- Neuroblastoma cells were treated with retinoids and analyzed using microarrays, RT-PCR, and flow cytometry.
- CD117 mRNA sequences were determined, and NB cell sensitivity to imatinib mesylate was tested.
Main Results:
- Retinoid treatment induced genes, including CYP26A1 and CYP26B1, and upregulated CD117 (KIT) expression.
- Upregulation of CD117 correlated with increased sensitivity to the kinase inhibitor imatinib mesylate.
- A polymorphism in CD117 mRNA was identified in SH-SY5Y NB cells.
Conclusions:
- Combining retinoids with kinase inhibitors may offer a promising therapeutic approach for neuroblastoma.
- Further research is warranted to explore this combination therapy in clinical settings.
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