• Evelyn Harris, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan
• Maya Kliewer, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan
• Jessica Sharpe, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan
• Behzad Toosi, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan

Osteosarcoma is a highly metastatic and lethal bone cancer in canines and humans. Even with an aggressive treatment consisting of amputation and chemotherapy, the average duration of survival is one-year post-treatment for dogs and only 60% of human patients survive longer than 5 years post-treatment. This study aims to better understand the pathophysiology of osteosarcoma with a focus on the role of the EphA2 receptor tyrosine kinase (RTK). EphA2 is one of nine members of the EphA RTK family and in the search for new targeted cancer therapies, EphA receptors are emerging as promising regulators of tumor development, invasiveness, and drug resistance. However, the expression and functional roles of EphA2 in canine and human osteosarcoma have not been investigated.

Our research has revealed an increased expression of EphA2 in canine and human osteosarcoma cells lines using Western blotting. To evaluate the functional relevance of overexpressed EphA2 in osteosarcoma cells, we silenced the expression of EphA2 using a specific shRNA. Silencing of EphA2 resulted in reduced proliferation, migration, and invasion of osteosarcoma cells in culture when compared with non-silenced control cells. Our results also revealed that after EphA2 silencing, osteosarcoma cells showed an increased sensitivity to a common chemotherapeutic drug, Cisplatin, in culture. EphA2 silencing also reduced tumor growth rate in a mouse xenograft model of dog osteosarcoma.

These data suggest that increased EphA2 function is a major driver of the malignant behavior of canine and human osteosarcoma and a promising target for the development of new therapies.