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Modulation of N-myc expression alters the invasiveness of neuroblastoma

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Abstract

N-myc oncogene expression plays a pivotal role in the biology of neuroblastoma, a common childhood tumor. High N-myc expression is associated with advanced disease stage, and in animal models, increased expression results in increased metastatic potential. In normal embryologic development, N-myc expression is associated with neuroblast migration out from the neural crest. To further define the relationship between N-myc and metastasis, an in vitro assay was adapted to measure tumor cell attachment, motility, and proteolytic ability in neuroblastoma cell lines. These parameters were examined in a non-amplified, uniformly N-myc overexpressing cell line and its anti-sense N-myc expressing clones. These lines have been characterized previously, and have a decrease in N-myc expression, growth rate, and tumorigenicity relative to the parent line and vector-only control transfectant. Decrease in N-myc expression resulted in a non-proportional increase of tumor cell attachment, and a proportional decrease in both tumor cell motility and proteolytic ability. In further experiments, assay of a N-myc-amplified overexpressing cell line with an intrinsic heterogeneous pattern of expression demonstrated that motile cells expressed higher amounts of N-myc relative to the general population. Together these relationships indicate that N-myc plays a causative role in the invasive phenotype, and suggest that metastasis may, in part, result from the disruption of a developmentally important normal process.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology/Oncology, UCLA School of Medicine, the Gwynne Hazen Cherry Memorial Laboratories, and the Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA

    Lisa A. Goodman, Joyce M. Yamashiro, David S. M. Pai & Randal K. Wada

  2. Department of Urology, Mount Sinai School of Medicine, New York, NY, USA

    Brian C. S. Liu

  3. Pediatric Branch, National Cancer Institute, Bethesda, MD, USA

    Carol J. Thiele

  4. Department of Pediatric Oncology, University of Illinois, Chicago, IL, USA

    Mary Lou Schmidt

  5. Department of Pediatrics, Childrens Memorial Hospital and Northwestern University, Chicago, IL, USA

    Susan L. Cohn

  6. Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Naohiko Ikegaki

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  1. Lisa A. Goodman
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  2. Brian C. S. Liu
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  3. Carol J. Thiele
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  4. Mary Lou Schmidt
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  9. Randal K. Wada
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Goodman, L.A., Liu, B.C.S., Thiele, C.J. et al. Modulation of N-myc expression alters the invasiveness of neuroblastoma. Clin Exp Metastasis 15, 130–139 (1997). https://doi.org/10.1023/A:1018448710006

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  • DOI: https://doi.org/10.1023/A:1018448710006

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