• Jessica Sharpe, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan
• Evelyn Harris, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan
• Tim Strozen, 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 aggressive bone cancer in canines and humans with a high rate of metastasis to the lungs and a poor prognosis. Advances in treatment options are limited and more effective therapeutic approaches need to be developed. The Eph receptors are the largest group of receptor tyrosine kinases, regulating many cellular activities including proliferation, survival, migration, and invasion. Recent evidence suggests that the EphB4 receptor is involved in the regulation of invasion and metastasis of various human cancers. However, the role of the EphB4 receptor in the fitness of human and canine osteosarcoma has been poorly evaluated. Due to the physiological and cellular similarity between canine and human osteosarcoma, we investigate the role of the EphB4 receptor in promoting osteosarcoma using a comparative approach.

We found upregulated expression of the EphB4 receptor in canine and human osteosarcoma cells as assessed by western blotting. EphB4 expression was silenced using specific shRNAs in multiple canine and human osteosarcoma cell lines. In both canine and human osteosarcoma, cells with silenced EphB4 reduced cell proliferation, migration, and invasion, increased sensitivity to cisplatin, and altered colony morphology in human osteosarcoma. Interestingly, both canine and human osteosarcoma cells with silenced EphB4 formed more tumorspheres suggesting an enhanced tumor-initiating potential.

The EphB4 receptor is overexpressed in both canine and human osteosarcoma and may regulate important processes in the development and invasiveness of the cancer. The similar results in both dog and human osteosarcoma emphasize the benefit of using a comparative oncology approach.