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Published on: May 25, 2018
Establishment and characterization of new orthotopic and metastatic neuroblastoma models
Estelle Daudigeos-Dubus1, Ludivine LE Dret1, Valérie Rouffiac2
1Vectorology and Anticancer Therapeutics, UMR 8203, University Paris-Sud, Orsay, France CNRS, Orsay, Vectorology and Anticancer Therapeutics, UMR 8203, Orsay, France Gustave Roussy Institute, Vectorology and Anticancer Therapeutics, UMR 8203, Villejuif, France.
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.
Insights
New preclinical models for stage 4 neuroblastoma were developed, showing distinct metastatic patterns. These models aid in studying tumor spread and evaluating new pediatric cancer therapies.
Area of Science:
- Pediatric Oncology
- Cancer Research
- Preclinical Models
Background:
- Metastatic neuroblastoma treatment is challenging.
- Effective preclinical models are crucial for understanding oncogenesis and developing new therapies.
- Stage 4 neuroblastoma models were developed to address this need.
Purpose of the Study:
- To develop and characterize novel orthotopic and metastatic preclinical models for stage 4 neuroblastoma.
- To investigate the metastatic tropism of neuroblastoma cell lines in vivo.
- To validate the utility of these models for evaluating antitumor responses.
Main Methods:
- Established orthotopic and systemic models in immunodeficient mice (BalbC Rag2(-/-)gammaC(-/-)).
- Utilized luciferase-transfected IMR-32 and IGR-N91 neuroblastoma cell lines.
- Administered cells via adrenal (orthotopic) and intravenous (systemic) injection.
Main Results:
- Achieved a 100% tumor take rate across all four developed models.
- Observed distinct metastatic patterns for orthotopic and systemic models, with specific organ tropisms identified for IMR-32-Luc and IGR-N91-Luc cells.
- Demonstrated the feasibility of non-invasive, real-time evaluation of antitumor responses in systemic models.
Conclusions:
- The developed neuroblastoma models exhibit unique metastatic spread patterns.
- These models serve as valuable tools for investigating tumor cell tropism and mechanisms of metastasis.
- They are suitable for evaluating the efficacy of novel cancer therapeutics in a preclinical setting.
