ENDOPEPTIDASE-24.11 ACTIVITY IN THE HUMAN PROSTATE-CANCER CELL-LINES LNCAP AND PPC-1

Human endopeptidase 24.11 (EP) occurs in greatest abundance on termina lly differentiated prostate cells; thus, loss of EP could mark dediffe rentiation of prostate epithelium. To identify laboratory models that would permit continuous work on the biochemistry and hormonal regulati on of EP, we examined the well-differentiated LNCaP and poorly differe ntiated PPC-1 human prostate cancer cell lines. Ultrastructural analys is revealed that LNCaP secretes electron-dense material that resembles the particulate matter of seminal plasma, which is associated with en dopeptidase activity. LNCaP medium contained EP activity while PPC-1 m edium did not. Whether the apparent deletion of EP from the PPC-I cell line is characteristic of poorly differentiated prostate adenocarcino ma is not yet clear. However, it may be relevant to the carcinogenic p rocess that EP can limit growth of lung small carcinomas by inactivati ng cell growth-promoting bombesin-like peptides. Because bombesin has been identified in aggressive human prostate cancers, loss of EP in PP C-1 could represent a necessary step in transformation to aggressive p henotype. The combination of LNCaP and PPC-1, which offers well-differ entiated and poorly differentiated cancer phenotypes, appears well sui ted to studying the relevance of EP in prostate cancer biology.