Establishment and characterization of new orthotopic and metastatic neuroblastoma models

In Vivo. 2014 Jul-Aug;28(4):425-34.


Background/aim: Treatment of metastatic neuroblastoma remains a challenge in pediatric oncology. Relevant preclinical models may improve exploration of oncogenesis and new therapies. We developed new orthotopic and metastatic models derived from stage 4 neuroblastoma.

Material and methods: Orthotopic and systemic models were established in BalbC Rag2(-/-)gammaC(-/-) mice following adrenal and intravenous injection of luciferase-transfected IMR-32 and IGR-N91 cells, respectively.

Results: All four models exhibited 100% tumor take rate. Metastatic spread of orthotopic IMR-32-Luc cells was observed mainly to the lung, liver and bone; that of IGR-N91-Luc cells to liver, spleen and adrenals. Interestingly, systemic IMR-32-Luc cells metastasized rather to the lung, liver and bone, and IGR-N91-Luc to liver, lung, spleen and adrenals. Feasibility of non-invasive, real-time antitumor response evaluation was validated in the systemic models.

Conclusion: These neuroblastoma models with distinct patterns of metastatic spread represent relevant tools for exploring local and metastatic tumor cell tropism, mechanisms of spread and evaluating new cancer therapeutics.

Keywords: Orthotopic and systemic human xenograft model; bioluminescence imaging; metastasis pattern; neuroblastoma.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Biopsy
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Disease Models, Animal*
  • Gene Expression
  • Genes, Reporter
  • Heterografts
  • Humans
  • Irinotecan
  • Luciferases / genetics
  • Luminescent Measurements / methods
  • Mice
  • Mice, Knockout
  • Neoplasm Metastasis
  • Neuroblastoma / diagnosis
  • Neuroblastoma / drug therapy
  • Neuroblastoma / genetics
  • Neuroblastoma / pathology*
  • Tumor Burden
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • Luciferases
  • Camptothecin