NUB-7: a stable I-type human neuroblastoma cell line inducible along N- and S-type cell lineages

Abstract

Human NB cell lines express features of one or more of three recognizable phenotypes that include N-type (neuroblastic), S-type (Schwannian), and I-type (intermediate phenotype) cells. The I-type cell, which shares properties of both N- and S-type cells, is thought to represent the progenitor cell from which the other two cell types are derived. The MYCN amplified NB cell line NUB-7, established in our laboratory, is now shown to be composed principally of I-type cells. The observed phenotype was stable in culture and was representative of the original surgically resected tumor. The I-type cell designation was established based on morphological characteristics, the coexpression of various N-type (neurofilaments, peripherin, GAP-43, NCAM, MYCN) and S-type cell (vimentin, laminin, fibronectin) markers, and the relatively high level of expression of these markers in comparison to five predominantly N-type, one S-type, and one N/S mixed NB cell lines. Dibutyryl cyclic AMP and retinoic acid induced enhanced expression of N- and S-type phenotypes, respectively, in NUB-7 as supported by specific morphological changes, reduced growth, and changes in the levels of expression of both N- and S-type markers. Our studies with the NUB-7 cell line have now provided convincing evidence for the existence of a bipotential progenitor of N- and S-type cells in NB. As well, the NUB-7 cell line may also represent the tumor counterpart of a sympathetic ganglion progenitor cell.