Osteosarcoma is a devastating disease which affects younger people at the most productive time of their lives. We seek to identify new weaknesses in osteosarcoma, which may lead to the development of new, effective therapies.
Chemotherapy has improved prognosis but has reached a plateau in terms of increasing survival. Identifying genes involved is key to developing drugs against this disease.
We identified that Wnt inhibitory factor-1 (WIF1), a secreted protein, is not expressed in the majority of human osteosarcoma samples. In mice deficient in Wif1 we found that bone development was normal, however these animals were predisposed to both spontaneous and radiocarcinogen induced osteosarcomas compared to control animals.
Further investigation of WIF1 found that re-expression of WIF1 in osteosarcoma cell lines stopped cell growth. We are currently investigating whether treatment with WIF1 can suppress tumour growth in mice. The results from our studies represent a significant step forward in understanding the role of WIF1 in bone development and tumourigenesis.
Secreted inhibitors have high therapeutic potential, and our hope is that these studies may eventually lead to the rational design of WIF1 mimetic agents to specifically inhibit tumour growth.