We are investigating the contributions of proteases and their inhibitors in prostate cancer progression in search of novel molecular markers and/or treatment targets. Our previous work has involved gene expression profiling of all matrix metalloproteases and several serine proteases in bulk fresh frozen prostate tissues from our extensive human tissue bank established at the Norfolk and Norwich University Hospital, established as a result of a collaboration between the university and the hospital. We are currently using laser capture microdissection to acquire populations of epithelial and stromal cells from a range of grades of tumours. Protease expression will be confirmed at the protein level using immunohistochemistry on tissue microarrays.
Using outcome data from our patient database, we aim to use some of these markers to molecularly stage patients or as therapeutic targets. The project will lead to further functional studies involving gene knockdown and overexpression in epithelial and stromal cell co-cultures and mouse models.