Neuroblastoma: Induction of differentiation (Part I) - Basical science in pediatric surgery

Neuroblastoma is the second-most common solid tumor in childhood. The major ity of patients have a very poor outcome due to aggressive growth and metas tatic spread. In contrast, in rare cases, spontaneous regression or differe ntiation towards a benign ganglioneuroma are observed, The mechanism leadin g to differentiation of neuroblastoma is of particular therapeutic interest . In this paper we report the results of our attempts to induce the express ion of genes necessary for differentiation of neuroblastoma cells. TrkA cod es for the high affinity receptor of NGF, a neurotrophin known to promote d ifferentiation. Treatment with retinoic acid caused a 3-fold increase of th e trkA expression in neuroblastoma cell lines. Neurofibromin, the gene prod uct 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 typ e II isoform of neurofibromin is predominantly expressed. Retinoic acid was able to raise the proportion of type II NF-1 expressed in neuroblastoma ce lls.