Maturation of cathepsin D as possible predictor of prostate cancer progression

Cathepsin D (Cat,D), an intracellular lysosomal protease, has been implicat ed in tumor invasion and metastasis. Expression and activity of the differe nt molecular forms of Cat,D have also been shown to be biologically and cli nically significant in tumor progression. Although several studies on Cat,D have been performed in prostate cancer using immunohistochemical analyses, the results were inconsistent. We thus reexamined the clinical relevance o f Cat,D in prostate cancer by Western immunoblot analysis using human prost ate tissues. These studies revealed that Cat,D was differentially expressed in a tissue-specific manner. Procathepsin D, a precursor of Cat.D, was a m ajor form expressed in normal (NML) and benign prostatic hyperplasia (BPH) specimens, while mature Cat,D was notably expressed in prostate cancer (CAP ) specimens. The catalytic activity of Cat,D was also consistently higher i n CAP than in NML/BPH specimens. Further studies showed that this high Cat, D activity in CAP often differed from specimen to specimen, and its activat ion was well associated with acid-induced self-degradation or autoproteolys is of mature Cat,D, Therefore, the different molecular forms and activity o f Cat,D may have significant clinical implications and could also be consid ered as a possible predictor of prostate cancer progression.