Human neuroblastoma cells growing in culture offer a unique opportunity to study proliferating human cells with a neuronal phenotype. We have previously identified several neuroblastoma cell lines which show spontaneous conversion (N/S interconversion) between two morphologically distinct cell types: neuroblastic (N-type) cells and variant, substrate-adherent (S-type) cells resembling cultured glial or mesenchymal cells. In the present study, we have used molecular markers to confirm the neuronal phenotype of N-type cells and to demonstrate that S-type cells have a nonneuronal phenotype. Furthermore, we have used these markers, including a series of cell surface differentiation antigens, to compare S-type neuroblastoma cells with a wide range of cultured epithelial, mesenchymal, and neuroectodermal cells. The results suggest that (a) N/S interconversion represents an ordered transition between two neuroectodermal differentiation programs rather than random phenotypic instability of cultured cells; (b) S-type variant cells show a molecular phenotype most closely resembling the phenotype of cultured ectomesenchymal cells; and (c) in vitro variant formation of human neuroblastomas may provide an experimental model for the observed in vivo transition of some malignant neuroblastomas into benign ganglioneuromas.

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This work was supported in part by grants from the National Cancer Institute (CA-08748, CA-31553), the Oliver S. and Jennie R. Donaldson Charitable Trust, and the Kleberg Foundation.

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