Expression of ADAMs (a disintegrin and metalloproteases) and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic adenocarcinomas

Abstract

A disintegrin and metalloproteases (ADAMs) are proteins that contain both a disintegrin and metalloprotease domain and have potential implications for the metastasis of human cancer cells via cell adhesion and protease activities. In this study, we analyzed the expression levels of ADAM-9, ADAM-10 and ADAM-17 (TNF-alpha converting enzyme, TACE), and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic tumor cell lines as well as in clinical patient materials (BPH and tumor tissue samples). Human prostatic tumor cell lines (MDA PCa 2b, LNCaP-C33, -C51, -C81, -Pro5, -Ln3, -C4-2, PC3, and DU145) showed varied levels of expression for ADAM-9, -10 and -17 mRNA. A strong expression of ADAM-17/TACE was further revealed by Western blot analysis in prostatic tumor cell lines. In the case of clinical material, all the tumor samples (8/8) revealed the expression of ADAM-9, -10, and -17 compared to the specimens of benign prostatic hyperplasia (BPH) where 80% of (8/10) samples showed the expression of ADAM-9, 86% (6/7) of ADAM-10, and 30% (3/10) of ADAM-17/TACE. Interestingly, expression of a potent inhibitor of ADAM-17 (TIMP-3) was not detected in any prostatic tumor cell lines (0/9), while TIMP-3 expression was detected in 82% (9/11) of BPH samples. Androgen-sensitive LNCaP-C33 cells exhibited differences in ADAMs regulation by 5alpha-dihydrotestosterone (DHT), while such differences were not detectable in androgen-independent LNCaP-C81 cells. These results suggest that an inverse expression pattern of ADAM-17/TACE and TIMP-3, and the regulation of ADAMs with DHT might play an important role in the pathogenesis of prostate cancer.