PROSTATE-SPECIFIC ANTIGEN, A SERINE-PROTEASE, FACILITATES HUMAN PROSTATE-CANCER CELL INVASION

Human prostatic epithelial cells constitutively secrete prostate-speci fic antigen (PSA), a kallikrein-like serine protease, which is a norma l component of the seminal plasma, PSA is currently used as a specific diagnostic marker for the early detection of prostate cancer, We demo nstrate that PSA degrades extracellular matrix glycoproteins fibronect in and laminin and, thus, may facilitate invasion by prostate cancer c ells, Blocking PSA proteolytic activity with PSA-specific mAb results in a dose-dependent decrease in vitro in the invasion of the reconstit uted basement membrane Matrigel by LNCaP human prostate carcinoma cell s which secrete high levels of PSA, A novel PSA-SDS-PAGE zymography me thod for the detection of matrix degrading ability of PSA is also desc ribed, We propose that: (a) because of the dysplastic cellular disorga nization in early neoplastic lesions called prostatic intraepithelial neoplasia (PIN), PSA may be secreted not only at the luminal end but a lso, abnormally, at the cell-basement membrane interface, causing matr ix degradation and facilitating invasion; and (b) PSA, along with urok inase, another serine protease secreted by prostatic epithelium, may b e involved in the proteolytic cascade during prostate cancer invasion and metastasis. The discovery of the extracellular matrix degrading ab ility of PSA not only makes it a marker for early detection but also a target for prevention and intervention in prostate cancer.