title: Retinoic acid-induced differentiation of human neuroblastoma: a cell variant system showing two distinct responses.
abstract: Retinoic acid (RA) has been shown to induce the differentiation of human neuroblastoma cells in vitro. In this study, we describe two variants of the SK-N-SH human neuroblastoma cell line that have dramatically different responses to RA. RA induces neuronal-like differentiation characterized by extensive neurite outgrowth, thick neurite bundles, and large cellular aggregates of SK-N-SH-N (SH-N) cells. In contrast, RA treatment of SK-N-SH-F (SH-F) cultures transforms the small neuroblast cells into large flattened, fibroblastic or epithelial-like cells. Karyotype analysis verified that the SH-N and SH-F cultures were derived from a common precursor cell. Confirmation of their markedly different responses to RA was obtained by metabolic labelling of glycoproteins and SDS-PAGE analysis. While both sublines showed very similar Coomassie-labelled protein bands and glycoprotein profiles in control cultures, dramatic differences between the lines were revealed following RA treatment. In contrast to their similar protein profiles, untreated SH-N and SH-F cells had quite different patterns of ganglioside biosynthesis in that GM3 was detected in SH-F cells but not in SH-N, while GM1 was only detected in SH-N. Cellular RA binding protein (CRABP) was detected in both SH-F and SH-N cells and their RA-transformed derivatives. These results demonstrate heterogeneity in the response to RA of neuroblastoma cells derived from a common origin that cannot be accounted for by differences in CRABP content. The SH-N and SH-F neuroblastoma sublines should provide a useful system for further studies of the molecular processes through which RA exerts its differentiation-inducing activity on this type of tumor.
mesh_terms: D002352:Carrier Proteins / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D005732:Gangliosides / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D007621:Karyotyping; D008970:Molecular Weight; D009447:Neuroblastoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D018168:Receptors, Retinoic Acid; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D005732:Gangliosides; D006023:Glycoproteins; D007527:Isoenzymes; D018168:Receptors, Retinoic Acid; D014212:Tretinoin