Estelle Daudigeos-Dubus1, Ludivine LE Dret1, Valérie Rouffiac2, Olivia Bawa3, Ingrid Leguerney4, Paule Opolon3, Gilles Vassal1, Birgit Geoerger5. 1. Vectorology 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. 2. Imaging and Cytometry Platform, UMR 8081 IR4M, Gustave Roussy Institute, Villejuif, France. 3. Plateform of Preclinical Evaluation, Gustave Roussy Institute, Villejuif, France. 4. IR4M, UMR 8081, Paris-Sud University, CNRS, Orsay, France. 5. Vectorology 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 Department of Pediatric and Adolescent Oncology, Gustave Roussy Institute, Villejuif, France birgit.geoerger@gustaveroussy.fr.
Abstract
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.
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.
Authors: Lan G Coffman; Daniela Burgos-Ojeda; Rong Wu; Kathleen Cho; Shoumei Bai; Ronald J Buckanovich Journal: Transl Res Date: 2016-03-30 Impact factor: 7.012
Authors: Julie H Harreld; Emily M Bratton; Sara M Federico; Xingyu Li; William Grover; Yimei Li; Natalie C Kerr; Matthew W Wilson; Mary E Hoehn Journal: Pediatr Blood Cancer Date: 2015-11-24 Impact factor: 3.167