Grant: Master's Award: Canada Graduate Scholarships

Breast cancer-related deaths result from tumour metastasis, to which angiogenesis is a key contributor. Peroxisome proliferator-activated receptor (PPAR?) activating drugs have both anti-breast tumourigenic and anti-angiogenic effects, but the role of PPAR? in breast tumour angiogenesis is unknown. I hypothesize that loss of PPAR? expression in endothelial cells (ECs) enhances breast tumour angiogenesis. I will first define the role of PPAR? in mammary ECs. Mammary ECs isolated from wild-type (WT) and EC targeted PPAR?-knockout (PPAR?-EC KO) mice, and human umbilical vein ECs (HUVECs) stably transfected with lentivirus containing p53 and control or PPAR?-short hairpin RNA plasmids, treated with or without the PPAR? activating drug rosiglitazone (ROSI) will be compared in vitro for angiogenic phenotypic and protein expression changes in PPAR?, vascular endothelial growth factor (VEGF), and VEGF receptors. Second, I will compare angiogenic sprouts formed in matrigel plugs injected into mammary fat pads of WT and PPAR?-EC KO mice to assess the in vivo angiogenic role of EC-specific PPAR?. Third, I will determine the role of EC-specific PPAR? expression during in vivo chemical carcinogen-induced breast tumourigenesis. Breast tumour outcomes and vascularity will be compared between WT and PPAR?-EC KO mice. Overall, these studies will define how EC-specific PPAR? expression influences angiogenesis during breast tumourigenesis, which may help improve therapeutic options for breast cancer patients.