DIFFERENTIATION OF HUMAN NEUROBLASTOMA CELLS IN VITRO — MORPHOLOGICAL CHANGES INDUCED BY DIBUTYRYL CYCLIC AMP

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Abstract
Differentiation ability of neuroblastoma cells was studied in vitro by light microscopy and EM using 3 continuously cultured cell lines (NB-1, GOTO and YT-nu) of human origin. The cells ordinarily cultured appeared to differentiate along directions of ganglionic and parganglionic cells in NB-1 and, scarcely, in YT-nu. Paraganglionic cells were characterized by cytoplasmic catecholamine granules measuring 150-250 m.mu. in diameter. Two-direction differentiation was induced by treatment with But2cAMP [dibutyryl cyclic AMP] in NB-1 and YT-nu cells, but GOTO cells revealed only 1-direction differentiation along ganglionic cells regardless of But2cAMP conditioning. Morphological and functional differentiation of mouse and human neuroblastoma cells in vitro, conversion of rat phenochromocytoma cells into sympathetic neurons in vitro and ultrastructural differentiation of human neuroblastoma in vivo were discussed. Neuroblastoma might be derived from a primitive stem cell of neural crest origin which possesses the pluripotency to be capable of differentiating along the sympathetic, parasympathetic, paraganglionic and other neural crest derivatives under certain conditions.