Grant: Master's Award: Canada Graduate Scholarships

The Effects of BMP-9 on Tumour Angiogenesis With and Without the Loss of Endothelial BMPR2 One ligand whose involvement in cancer requires more study is bone morphogenetic protein 9 (BMP-9). BMP-9 is involved in both normal and pathogenic angiogenesis, normally acting as a quiescence factor to suppress vascular growth. BMP-9 signals through binding Bone Morphogenetic Protein Receptor II (gene: BMPR2), however it is promiscuous, which may lead to bidirectional effects on angiogenesis. Although previous research on the role of BMP-9 in cancer has been conducted, the results have been contradictory. To fill in the gaps in current knowledge, the overarching question being explored in this proposed research is, “Does the loss of BMPR2 influence the contribution of BMP-9 to the vascularization of solid tumours?” The current proposal is based on the hypothesis that BMP-9 suppresses angiogenesis under normal conditions but promotes endothelial cell proliferation when BMPR2 is down-regulated or lost. The main challenges with previous studies addressing this question are associated with the fact that many tumour models are also responsive to BMP-9. This makes it impossible to determine if responses to treatment are due to the influence of BMP-9 on tumour vascularization or a direct action of the ligand on tumour growth. The current proposal will address this question through the targeted deletion of BMPR2 in either the vasculature or the tumour of an in vivo metastatic breast cancer model. This project will give insight into the effects of BMP-9 on pathogenic angiogenesis and whether its effects are modified with the loss of endothelial BMPR2. A new role of BMP-9 may be identified which could lead to the discovery of potential new pathways to target during cancer treatment.