An Exploratory Genetic Model Study for the Role of Osteopontin in Rhabdomyosarcoma Subtypes

Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma found in children, with distinct biological subtypes. We found that the protein Osteopontin (Ostp) is highly expressed in our genetically engineered mouse models (GEMM) of RMS alveolar and embryonal subtypes. Through GEMM studies and allograft mouse studies we explored how Ostp expression affects the onset and growth of tumors in vivo. Ostp loss in alveolar RMS tumors and the tumor microenvironment of genetically-engineered mice changed the character of the tumors (decreasing multiplicity, decreasing limb predominance, and decreasing tumor stage) without changing tumor-free survival or histological appearance. Similarly, tumor growth rates and metastasis were not different for Ostp expressing and Ostp null tumors in orthotopic allograft studies. Conversely, loss of Ostp expression increased tumor incidence in embryonal RMS GEMMs animals compared to mice on an Ostp wildtype background, although the sample size was small. When combined with the clinical correlation of human Osteopontin gene expression and altered patient survival, Ostp in embryonal RMS may be a topic of further interest and investigation.