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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

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
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/glioma.glioma_3_18

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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.

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