Evidence of protein C inhibitor in prostatic carcinoma
Prostate tumor cell invasion and metastasis involves numerous concerted interactions between both cellular and stromal components, including proteinases and their interactions with proteinase inhibitors. Protein C Inhibitor (PCI), also called plasminogen activator inhlbitor-3 (PAI-3), is a member of the serine proteinase inhibitor (serpin) superfamily. PCI inhibits proteinases found in the prostate such as thrombin, activated protein C, urokinase-type plasminogen activator, and prostate specific antigen which are Important during blood coagulation, wound repair, and cell migration processes. By Northern Mot analysis, PCI mRNA was found as expected in many human tissues including the liver, kidney, testis, and prostate, but unexpectedly in the spleen, pancreas, and ovary. PCI mRNA was also detected in paired hyperplastic and malignant samples from five men with prostate cancer. PCI was localized to normal human prostatlc epithelial cells by immunohistochemistry. There appeared to be an increase in PCI immunoreactivity in both hyperplastic and malignant tissue (scored with Gleason grades of III and IV). The increase In PCI staining in malignant tissue was evident in surrounding stroma, possibly due to breakdown of the tubulo-acinar glands' structural integrity. Furthermore, a prostatlc carcinoma cell line, PC-3, was found to express PCI de novo. These results indicate that PCI is present in normal and neoplastic prostate. PCI inhibits prostate-related proteinases and may have a role in regulating the "proteolytic cascade" which facilitates prostatic metastasis.
Neese, LL; Cooner, ST; Jackson, TP; DiCuccio, MN; Hoffman, M; Church, EC
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