Abstract 1929: A novel orthotopic mouse model in sarcomas

Pediatric sarcomas are a heterogeneous group of bone and soft tissue malignancies affecting children and young adults. 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 consists in injecting Ewing Sarcoma (ES) or Rhabdomyosarcoma (RMS) tumor cells at the gastrocnemius muscle of mice and extracting the tumor at a of 10 mm x 13 mm volume. After surgery, animals maintain a complete functional extremity and can live until lung metastasis detection (about 60 days post-injection). Moreover, we have validated the suitability of the model with an Ewing Sarcoma EphA2-low expression cell line. Epha2 is a tyrosine kinase receptor that has been found overexpressed in a wide variety of tumors and correlated with malignant phenotype. In this study we report that EphA2 receptor is phosphorylated at S897 in a panel of ES cell lines, which is related to the oncogenic properties of the receptor. Stable silencing of EphA2 in two different ES cell lines resulted in a decrease in the clonogenic, proliferation, migration and invasion capacity in vitro. Moreover, we performed an experimental metastasis assay, injecting tumor cells through the tail vain of mice and observed a reduction in the lung metastasis incidence in EphA2 silenced cells. We then used this new orthotopic metastasis model to validate the impairment in the invasion capacity of EphA2 silenced cells and confirm the decrease in lung metastasis incidence, indicating an oncogenic role for EphA2 in ES. This novel orthotopic metastasis model is a valuable tool both for the study of spontaneous metastasis and also for evaluating therapeutic index in the onset of metastasis, which can also be applied to the study of other pedriatric sarcomas. Citation Format: Silvia Garcia Monclús, Juan Huertas Martínez, Laura Lagares Tena, Santiago Rello Varona, Olga Almacellas Rabaiget, David Herrero Martin, Roser López Alemany, Oscar Martinez Tirado. A novel orthotopic mouse model in sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1929. doi:10.1158/1538-7445.AM2017-1929