Role of WIF1 in bone development and cancer
Osteosarcoma is the most common primary bone cancer and the third most common cancer in adolescents. Treatment often entails aggressive surgery with intensive chemotherapy, and causes life-long morbidity. The 5-year survival of patients with metastatic or recurrent disease is less than 25%. We do not understand the complex events which lead to the development of bone cancer. We have found that Wnt inhibitory factor 1 (WIF1), a secreted protein inhibitor of a cell growth pathway to be down regulated in osteosarcoma. Thus loss of WIF1 may allow cancer cells to survive or grow more rapidly. The aim of our studies are to investigate the role of WIF1 on bone development and cancer. Using cell lines and primary normal human bone cells, we will knockdown expression of WIF1 and examine whether these cells can undergo normal development. We will also examine how re-expressing WIF1 in bone cancer cells or treatment with WIF1 protein affects cancer cell growth and survival. We have obtained mice, which have no WIF1 expression and we will examine development and bone cancer growth in these animals. In addition, we will investigate how bone cancer cells lose expression of WIF1. These studies should give us insight into the role of WIF1 in bone development and cancer and may form the basis for the development of drug targets to bone cancer.
Dr David Thomas, A/Professor Paul Simmons
Cancer Council Research Grant
Peter MacCallum Cancer Centre
Award / Duration
Research Grant: 2007-2009