A novel orthotopic mouse model in sarcomas

Introduction: Pediatric sarcomas are a heterogeneous group of bone and soft tissue malignancies affecting children and young adults. Some of these highly aggressive tumors of mesenchymal origin harbor a characteristic chromosomal translocation. One of the most important prognostic factors of those diseases is the presence of metastasis at diagnosis. In that context, we have developed a novel orthotopic model, which can be used both for the study of spontaneous metastasis and also for evaluating therapeutic index in the onset of metastasis.

Methods: Orthotopic mouse model.

Results: This new model consists in injecting tumor cells at the gastrocnemius muscle of posterior extremity and extracting the primary tumor once it has reached a volume of 10 mm x 13 mm. After surgery, animals maintain a complete functional extremity and could live until lung metastasis detection. This model is more physiological than the classical experimental metastasis assay using tail-vein injection and can be used for the study of sarcomas such as Ewing sarcoma (ES), rhabdomyosarcoma (RMS) or osteosarcoma (OS). Using this orthotopic model, we have demonstrated the implication of a membrane receptor during the metastatic process in ES.

Conclusion: This technique provides not only a valuable tool for the study of cellular components implicated in the metastatic process but also a new system to test drug efficiency.