PMID- 7794812 OWN - NLM STAT- MEDLINE DCOM- 19950803 LR - 20131121 IS - 1044-9523 (Print) IS - 1044-9523 (Linking) VI - 6 IP - 4 DP - 1995 Apr TI - Human neuroblastoma I-type cells are malignant neural crest stem cells. PG - 449-56 AB - Human neuroblastoma I-type cells isolated from cell lines in vitro are morphologically intermediate between neuroblastic (N) cells, with properties of embryonic sympathoblasts, and substrate-adherent (S) cells having properties of embryonic Schwann/glial/melanocytic cells of the neural crest. I cells have biochemical features of both N and S cells. We propose that the I-type cell represents a malignant neural crest stem cell. The strongest evidence in support of this hypothesis is that: (a) I cells can generate progeny that have neuronal properties, i.e., are committed neuroblasts, or properties of nonneuronal, embryonic neural crest-derived cells; and (b) I-type cells can generate multipotent I-type progeny, indicating their capacity for self-renewal, a feature of stem cells. We report here that I-type cells, derived from four different human neuroblastoma cell lines and experimentally induced to differentiate, give rise to cells with distinct N or S cell phenotypes, indicative of I cell multipotentiality. Experiments with a large panel of I-type subclones, isolated from clonal I-type BE(2)-C cells and exposed to retinoic acid to induce neuronal differentiation or 5-bromo-2'-deoxyuridine to obtain S-type cells, demonstrated that differentiation occurs via induction and selection and not by selection of spontaneously arising variants. The differentiation phenotype was stable. We conclude that human neuroblastoma I-type cells are multipotent embryonic precursor cells of the peripheral nervous system, capable of either neuronal or nonneuronal neural crest cell differentiation. FAU - Ross, R A AU - Ross RA AD - Department of Biological Sciences, Fordham University, Bronx, New York 10458, USA. FAU - Spengler, B A AU - Spengler BA FAU - Domenech, C AU - Domenech C FAU - Porubcin, M AU - Porubcin M FAU - Rettig, W J AU - Rettig WJ FAU - Biedler, J L AU - Biedler JL LA - eng GR - CA08748/CA/NCI NIH HHS/United States GR - CA41520/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cell Growth Differ JT - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research JID - 9100024 RN - 5688UTC01R (Tretinoin) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Bromodeoxyuridine/pharmacology MH - Cell Differentiation/drug effects MH - Cell Transformation, Neoplastic MH - Clone Cells MH - Humans MH - Neural Crest/*pathology MH - Neuroblastoma/*pathology MH - Stem Cells/drug effects/*pathology MH - Tretinoin/pharmacology EDAT- 1995/04/01 00:00 MHDA- 1995/04/01 00:01 CRDT- 1995/04/01 00:00 PHST- 1995/04/01 00:00 [pubmed] PHST- 1995/04/01 00:01 [medline] PHST- 1995/04/01 00:00 [entrez] PST - ppublish SO - Cell Growth Differ. 1995 Apr;6(4):449-56.