Neoplastic chromaffin cells from human pheochromocytomas can exhibit extensive spontaneous and nerve growth factor (NGF)-induced outgrowth of neurite-like processes in vitro, despite the absence of such processes in vivo. To determine whether acquisition of neuron-like features by human pheochromocytoma cells in culture is accompanied by functional alterations, process outgrowth, vasoactive intestinal peptide-like immunoreactivity (VIPLI), neurotensin-like immunoreactivity (NTLI), and

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... ine content were studied in freshly dissociated cells and in 21day-old cultures from six human pheochromocytomas. All of the cultures produced VIPLI and exhibited spontaneous process outgrowth. NGF stimulated process outgrowth and enhanced production of VIPLI. Dexamethasone inhibited process outgrowth and tended to decrease production of VIPLI. NTLI was detected in cells from only one of the tumors, and its production appeared to be regulated comparably to that of VIPLI. Catecholamine content decreased markedly in all of the cultures and was not regulated in parallel with either VIPLI or NTLI. The findings suggest that human pheochromocytoma cultures may help to elucidate cellular and molecular mechanisms regulating ectopic and normal VIP production.