Neuroblastoma: induction of differentiation (Part I). Basical science in pediatric surgery

Neuroblastoma is the second-most common solid tumor in childhood. The majority of patients have a very poor outcome due to aggressive growth and metastatic spread. In contrast, in rare cases, spontaneous regression or differentiation towards a benign ganglioneuroma are observed. The mechanism leading to differentiation of neuroblastoma is of particular therapeutic interest. In this paper we report the results of our attempts to induce the expression of genes necessary for differentiation of neuroblastoma cells. TrkA codes for the high affinity receptor of NGF, a neurotrophin known to promote differentiation. Treatment with retinoic acid caused a 3-fold increase of the trkA expression in neuroblastoma cell lines. Neurofibromin, the gene product of the NF-1 gene, is involved in downregulation of the activity of ras-proteins. In contrast to immature neuronal tissues in mature brain, the type II isoform of neurofibromin is predominantly expressed. Retinoic acid was able to raise the proportion of type II NF-1 expressed in neuroblastoma cells.