Acquisition of neuron-like electrophysiological properties in neuroblastoma cells by controlled expression of NDM29 ncRNA
Article first published online: 20 OCT 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 119, Issue 5, pages 989–1001, December 2011
How to Cite
Gavazzo, P., Vella, S., Marchetti, C., Nizzari, M., Cancedda, R. and Pagano, A. (2011), Acquisition of neuron-like electrophysiological properties in neuroblastoma cells by controlled expression of NDM29 ncRNA. Journal of Neurochemistry, 119: 989–1001. doi: 10.1111/j.1471-4159.2011.07492.x
- Issue published online: 14 NOV 2011
- Article first published online: 20 OCT 2011
- Accepted manuscript online: 20 SEP 2011 04:40PM EST
- Received August 17, 2011; accepted September 5, 2011.
- GABAA receptors;
- neuroblastoma differentation;
- RNA polymerase III;
- tetrodotoxin-sensitive Na+ current;
- voltage-activated K+ current
J. Neurochem. (2011) 119, 989–1001.
Neuroblastoma is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumor nodules. It has been previously shown that the over-expression of a specific non-coding RNA, NDM29, reduces neuroblastoma development promoting cell differentiation. We have used neuroblastoma cells expressing NDM29 at its basal level (Mock cells) or at 5.4-fold higher levels (S1 cells) to investigate whether a functional differentiation correlates with morphological and biochemical development induced by NDM29 expression. First, analyzing the expression of specific markers we demonstrated that NDM29 expression is accompanied by a well coordinated differentiation process toward a neuron-like, rather than toward a glial-like, phenotype. Next, we defined the neuron-like traits of S1 in terms of secretion of cytokines involved in axon guidance, synapse formation and neurite outgrowth. Finally, we characterized the ionic channel apparatus of S1 cells by patch-clamp technique and compared with the Mock counterpart. S1 cells showed much higher levels of fast inactivating Na+ current and were able to generate mature action potentials. Moreover, they developed expression of functional GABAA receptors on their membrane. In contrast, the two cell lines shared very similar pools of functional K+ channels, although slight quantitative differences can be described. Our results suggest that a maturation occurs in neuroblastoma as a consequence of NDM29 expression, inducing the appearance of neuronal-like properties. In this context, S1 cells may represent a novel in vitro tool for electrophysiological and pharmacological studies of human cells of the neural lineage.