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Clinical & Experimental Metastasis

, Volume 15, Issue 2, pp 130–139 | Cite as

Modulation of N-myc expression alters the invasiveness of neuroblastoma

  • Lisa A. Goodman
  • Brian C. S. Liu
  • Carol J. Thiele
  • Mary Lou Schmidt
  • Susan L. Cohn
  • Joyce M. Yamashiro
  • David S. M. Pai
  • Naohiko Ikegaki
  • Randal K. Wada
Article

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.

invasion motility neuroblastoma N-myc 

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Copyright information

© Chapman and Hall 1997

Authors and Affiliations

  • Lisa A. Goodman
    • 1
  • Brian C. S. Liu
    • 2
  • Carol J. Thiele
    • 3
  • Mary Lou Schmidt
    • 4
  • Susan L. Cohn
    • 5
  • Joyce M. Yamashiro
    • 1
  • David S. M. Pai
    • 1
  • Naohiko Ikegaki
    • 6
  • Randal K. Wada
    • 1
  1. 1.Department of Pediatrics, Division of Hematology/OncologyUCLA School of Medicine, the Gwynne Hazen Cherry Memorial Laboratories, and the Jonsson Comprehensive Cancer CenterLos AngelesUSA
  2. 2.Department of UrologyMount Sinai School of MedicineNew YorkUSA
  3. 3.Pediatric BranchNational Cancer InstituteBethesdaUSA
  4. 4.Department of Pediatric OncologyUniversity of IllinoisChicagoUSA
  5. 5.Department of PediatricsChildrens Memorial Hospital and Northwestern UniversityChicagoUSA
  6. 6.Department of Human GeneticsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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