Morphological and biochemical modifications during neuroblastoma cell differentiation.

In order to define some distinctive criteria of differentiation, we studied the effects of retinoic acid (RA), γ-interferon (γ-IFN), cytosine arabinoside (ARA-C), nerve growth factor (NGF), tumor necrosis factor (TNF), and 12-0-tetradecanoylphorbol-13 acetate (TPA) on the human neuroblastoma cell line, LAN-5. Intracellular levels of acetylcholinesterase, neuron specific enolase, catecholamines, and related neurotransmitters were evaluated after 8 days of treatment with various inducers. Our data indicate that the most striking biochemical changes accompanying LAN-5 cell differentiation are a shift from a catecholaminergic to a cholinergic phenotype, and/or a drastic increase in the catecholamines levels. Moreover, small changes may be independent of thein vitro maturation. Thus, biochemical phenotyping, more than morphological evaluation, is a fruitful approach to monitor neuronal cell differentiation.