The role of COX-2 in maintaining cancer stem cells in osteosarcoma

Osteosarcoma is the most common primary bone cancer in children and dogs. It is an aggressive tumour with a rapid clinical course leading ultimately to metastasis. The expression of cyclooxygenase-2 (COX-2) has been linked to tumorigenesis, angiogenesis, resistance to apoptosis, cancer cell proliferation and metastasis. Both canine and human osteosarcoma has been shown to contain a subpopulation of cancer stem cells (CSCs) which overexpress COX-2 and may drive tumour growth, recurrence and metastasis. COX-2 inhibition using COX inhibitors appears to block the reversion of cancer cells to a CSC phenotype suggesting a major role in cancer initiation. I seek to further explore the role of the COX-2 pathway in tumour initiation and maintenance of the CSC phenotype in canine and human osteosarcoma by suppressing COX-2 expression using RNA interference. Exploration of this pathway in canine disease will offer the potential to develop a strong pre-clinical model for human Osteosarcoma therapeutics.