Lab Invest. 1992 Feb;66(2):143-51.

Dynamic model of differentiation in Ewing's sarcoma cells. Comparative analysis of morphologic, immunocytochemical, and oncogene expression parameters.

Laboratory investigation; a journal of technical methods and pathology

R Noguera, T J Triche, S Navarro, M Tsokos, A Llombart-Bosch

PMID: 1310513

Abstract

We report the establishment of a model of neural differentiation in four well-characterized Ewing's sarcoma cell lines. This process was induced by serum-depleted medium (1% fetal bovine serum) and agents such as dibutyryl cyclic AMP and retinoic acid. The morphologic changes were characterized predominantly by the presence of neurite-like elongated processes showing varicosities and branching along their course with numerous internal filaments and electron-dense granules. Immunocytochemically, differentiation was accompanied by a considerable increase in reactivity for neural markers of several types: neuroblastic, neuroepithelial, neuroendocrine, Schwannian and even glial. In contrast, the tumor promoter, phorbol 12-myristate 13-acetate inhibited differentiation. Several morphologic changes were observed in phorbol 12-myristate 13-acetate-treated cells: the cells became smaller and rounder, were poorly adherent to substrate, by electron microscopy lacked cytoplasmic organelles, electron-dense granules or neural processes, and showed decreased expression of neural markers. Northern blot analysis was performed to establish whether there was any relationship between neural differentiation and degree of N-myc, c-myc and dbl oncogene expression. There was no N-myc oncogene expression in the mRNA of Ewing's sarcoma cells, even after neural induced differentiation. The degree of c-myc and dbl oncogene expression appeared heterogeneous, and varied with the culture condition. Based on these results, it may be inferred that Ewing's sarcoma cells in vitro display a variable neural phenotype, there being a variety of biologic responses to diverse culture media and various differentiation agents, but with no consistent effect on N-myc, c-myc and dbl oncogene expression.

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Substances

• Culture Media, Serum-Free
• Tretinoin
• Bucladesine
• Tetradecanoylphorbol Acetate

MeSH terms

• Bucladesine / pharmacology
• Cell Differentiation / drug effects
• Culture Media, Serum-Free / pharmacology
• Gene Expression
• Humans
• Immunohistochemistry
• Neurons / cytology
• Oncogenes
• Sarcoma, Ewing* / genetics
• Sarcoma, Ewing* / immunology
• Sarcoma, Ewing* / pathology
• Tetradecanoylphorbol Acetate / pharmacology
• Tretinoin / pharmacology
• Tumor Cells, Cultured

Publication Types

• Comparative Study
• Journal Article
• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, Non-P.H.S.

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