Establishment and characterization of new orthotopic and metastatic neuroblastoma models

• Published in: In vivo (Athens) Vol. 28; no. 4; pp. 425 - 434
• Main Authors: Daudigeos-Dubus, Estelle, LE Dret, Ludivine, Rouffiac, Valérie, Bawa, Olivia, Leguerney, Ingrid, Opolon, Paule, Vassal, Gilles, Geoerger, Birgit
• Format: Journal Article
• Language: English
• Published: Greece 01-07-2014
• Subjects: 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; 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; bioluminescence imaging; neuroblastoma; Orthotopic and systemic human xenograft model; metastasis pattern
• ISSN: 1791-7549

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.
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.
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.
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.