Human neuroblastoma I-type cells are malignant neural crest stem cells Journal Article


Authors: Ross, R. A.; Spengler, B. A.; Domenech, C.; Porubcin, M.; Rettig, W. J.; Biedler, J. L.
Article Title: Human neuroblastoma I-type cells are malignant neural crest stem cells
Abstract: 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.
Keywords: morphology; medulloblastoma; differentiation; expression; n-myc; growth; lines; variants; proto-oncogenes; blastoma cells
Journal Title: Cell Growth & Differentiation
Volume: 6
Issue: 4
ISSN: 1044-9523
Publisher: American Association for Cancer Research  
Date Published: 1995-04-01
Start Page: 449
End Page: 456
Language: English
ACCESSION: WOS:A1995QR29000010
PROVIDER: wos
PUBMED: 7794812
Notes: Article -- Source: Wos
Citation Impact
MSK Authors
  1. June   Biedler
    83 Biedler
  2. Wolfgang J. Rettig
    85 Rettig