Two morphologically distinct types of cells have been observed in cultures of human neuroblastoma cells. One, designated N-type, is composed of small neuroblast-like cells; the other, designated S-type, is composed of large, substrate-adherent cells. To obtain additional information on the nature of these two phenotypes, we have investigated the collagen biosynthesis in several clones of human neuroblastoma cells with N-type, S-type, or mixed morphology, using acrylamide gel electrophoresis, ion exchange chromatography, and Northern and Southern blots. A direct correlation between the proportion of cells with S-type morphology and the amount of collagen secreted was observed, with the largest amount of collagen being produced by clones composed exclusively of S-type cells. Type I trimer and type III collagens were the two major isotypes secreted by these cells. The absence of secretion of the α2(I) collagen chain was associated with absence of RNA coding for this protein chain. The pro-α2 gene of type I collagen was found highly methylated in these cells.

Our data indicate that the presence of S-type cells in neuroblastoma cultures represents a differentiation of these neural crest-derived neuroblastic cells into glial cells such as Schwann cells.

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Supported by Grant CA 29397-01 from the National Cancer Institute and the Concern II Foundation (Y. A. D., E. T. B.) and Grants CA 31553 and CA 08748 (B. A. S., J. L. B.).

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