A series of neuroepithelioma and
neuroblastoma cell lines were screened for
nerve growth factor (
NGF)-induced differentiation. All three neuroepithelioma cell lines and all nine
neuroblastoma cell lines with amplified N-myc oncogene did not show any apparent
NGF-induced differentiation. However, neurite extension was observed for three of six
neuroblastoma cell lines with single-copy N-myc oncogene. The three responsive lines had a neuronal phenotype (short processes) which was enhanced by the addition of
NGF. The three nonresponsive cell lines were flat without any processes. The addition of
NGF to the responsive cell lines resulted in an up-regulation of neurofilament
mRNA expression.
Peripherin and
synapsin, two markers of terminal neuronal differentiation, were not induced. There was little effect of
NGF on the rate of cell growth or colony formation on soft
agar. Binding of
NGF to eight of the cell lines was analyzed by the method of Scatchard. Two responsive
neuroblastoma cell lines and one nonresponsive neuroepithelioma cell line expressed both low- and high-affinity binding sites. Two nonresponsive
neuroblastoma cell lines expressed only a small number of high-affinity binding sites, and two other nonresponsive
neuroblastoma cell lines did not detectably bind
NGF. Hence,
NGF-induced differentiation is confined to a particular class of neural-related
tumors, and, even for these cell lines, differentiation is incomplete.