Glioma

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 1  |  Issue : 2  |  Page : 66--78

Reprogramming glioma cell cultures with retinoic acid: Additional arguments for reappraising the potential of retinoic acid in the context of personalized glioma therapy


Matthieu Dreyfus1, Michèle El-Atifi2, Magali Court1, Marie Bidart3, Charles Coutton2, Céline Leclech1, Bruno Ballester1, Emmanuel Garcion4, Ali Bouamrani5, François Berger3, Didier Wion1 
1 INSERM UMR1205, 2280 Rue de la Piscine F, Saint Martin d'Héres, France
2 INSERM UMR1205, 2280 Rue de la Piscine F, Saint Martin d'Héres; CHU Michallon, La Tronche, France
3 INSERM UMR1205, 2280 Rue de la Piscine F, Saint Martin d'Heres; CHU Michallon, La Tronche; Universite Grenoble Alpes, Saint-Martin-d'Heres, France
4 CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France
5 Clinatec, CEA, Rue des Martyrs, Grenoble, France

Correspondence Address:
Dr. Didier Wion
Inserm UMR1205, 2280 Rue de la Piscine F - 38400 Saint Martin d'Heres
France

Background: Glioma, notably glioblastoma multiforme, is characterized by extensive inter-and intra-tumoral heterogeneity. Surprisingly, the potential for differentiation of glioma cells has not been systematically analyzed and included in patient stratification methods. In the current study, retinoic acid (RA), a neuronal differentiation agent, was assessed for the pro-differentiative and anti-proliferative effects on glioma cells. Methods: Using RA-responsive glioma culture as an experimental paradigm, we analyzed the differentiation process both by videomicroscopy and at the mRNA (RNA-seq and reverse transcription-quantitative-polymerase chain reaction) and proteomic levels. Results: Glioma cells can differentiate into neurons in response to RA by (i) extending ultra-long cytoplasmic extensions, (ii) using these extensions to move from cell to cell either by perikaryal translocation or in a "spider-flight" like process, (iii) slowing their cell cycling, (iv) acquiring several neuronal differentiation markers such as MAPT, GAP43, DCX, NRCAM, NeuroD2, NeuroG2, and NeuN, and (v) decreasing the expression of several genes associated with glioma aggressiveness. Conclusion: These results indicate the existence of a subgroup of patients harboring RA-responsive glioma cells amenable to differentiation therapy, and stratifying such patients with a functional test is easily achievable. This provides the first step to reassess the potential of RA in the context of personalized medicine.


How to cite this article:
Dreyfus M, El-Atifi M, Court M, Bidart M, Coutton C, Leclech C, Ballester B, Garcion E, Bouamrani A, Berger F, Wion D. Reprogramming glioma cell cultures with retinoic acid: Additional arguments for reappraising the potential of retinoic acid in the context of personalized glioma therapy.Glioma 2018;1:66-78


How to cite this URL:
Dreyfus M, El-Atifi M, Court M, Bidart M, Coutton C, Leclech C, Ballester B, Garcion E, Bouamrani A, Berger F, Wion D. Reprogramming glioma cell cultures with retinoic acid: Additional arguments for reappraising the potential of retinoic acid in the context of personalized glioma therapy. Glioma [serial online] 2018 [cited 2022 Aug 13 ];1:66-78
Available from: http://www.jglioma.com/article.asp?issn=2589-6113;year=2018;volume=1;issue=2;spage=66;epage=78;aulast=Dreyfus;type=0