Wilson, Michael J., Ph.D.

CANCER RESEARCH/PATHOBIOLOGY

Aging in men is marked by two diseases of abnormal growth in the prostate gland. One of these is a benign growth, whereas the other is cancer. My research endeavors are to understand: • How such growths start • The means by which abnormal tissue organization is established • How tumor cells are able to spread beyond the gland. We have been studying the role of certain proteases (enzymes that cleave proteins) in the tissue "remodeling" that occurs during generation of these pathologies. The proteases we have studied are found in different kinds of cells and different parts of these cells; they include plasminogen activators and matrix metalloproteases. To understand how these proteases may mediate changes in tissue organization, we study them in different growth situations as found in prostate tissues obtained at prostatectomy surgeries and in human prostate cancer cells grown in culture and implanted in nude mice. From our research it is becoming clear that it is not just the total activity of these proteases that is important in tissue organization changes with altered growth, but changes in the production of endogenous inhibitors to these proteases as well as changes in the subcellular localization and the cell type expressing them. We are also studying the role of certain peptidases that can cleave bioactive and growth promoting peptides in prostate function and pathology. In addition, we are examining the possible use of these peptidases as indicators of the onset and extent of prostate cancer in difference to benign hyperplasia of the prostate. We have shown the exclusive or near exclusive prostatic origin of angiotensin converting enzyme, leucine aminopeptidase, neprilysin, and dipeptidylpeptidase IV in human seminal plasma. We feel that since the prostate contributes about 25% of the total semen volume, that seminal plasma would be a good source to identify prostate derived molecules that would be related to prostate disease.