Establishment and characterization of new orthotopic and metastatic neuroblastoma models

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.