mRNA expression of the five membrane-type matrix metalloproteinases MT1-MT5 in human prostatic cell lines and their down-regulation in human malignant prostatic tissue.

BACKGROUND: The aim of this study was to assess the expression of membrane-type matrix metalloproteinases (MT-MMPs) 1-5 in the human prostatic cell lines BPH-1, LNCaP, DU 145, PC-3, in malignant and non-malignant prostatic tissue samples, and in epithelial cells cultured from these tissue samples. METHODS: Matched malignant and non-malignant tissue specimens were obtained from 12 men with untreated prostate carcinoma after radical prostatectomy. Expression of mRNA for the five MT-MMPs was quantified by real-time PCR technique and normalized to the expression of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RESULTS: The expression of the five MT-MMPs was distinctly different not only between the prostate cell lines but also varied in the same cell line. There was a general higher expression of all MT-MMPs except for MT3-MMP in the androgen-insensitive cells DU 145 and PC-3 compared with that in the androgen-sensitive LNCaP cells. Their relatively high expression in the benign prostatic cell line BPH-1 and also in the primary cell cultures from malignant and non-malignant tissue samples argues against a simple association between MT-MMP expression and invasiveness. In malignant tissue samples and their corresponding cell cultures, the expression of most MT-MMPs was down-regulated in comparison to the normal counterparts. There was no correlation between tumor classification data and the MT-MMP expression results. CONCLUSIONS: In contrast to other carcinoma, the down-regulation of most MT-MMPs is typical for prostate carcinoma. It seems to occur mainly in epithelial cells and has to be examined as special characteristic of this tumor entity in further studies.

Plasma matrix metalloproteinase 9 as biomarker of prostate cancer progression in Dunning (Copenhagen) rats.

BACKGROUND: Matrix metalloproteinases (MMPs) play an important role in invasion and metastatic spread of cancer cells. The objective of this study was to assess MMPs in plasma of Dunning tumor rats as indicators of the progression of prostate cancer and follow-up parameters after treatment. METHODS: Prostate cancer was induced in male Copenhagen rats by either subcutaneous or orthotopic implantation of R3327-MatLyLu cells. During the development of the tumor, plasma MMP-2, and MMP-9 were measured by gelatin-substrate zymography and Western blot technique with densitometry in untreated animals, rats treated with laser-induced hyperthermia, or with the new synthetic MMP inhibitor RO 28-2653. RESULTS: Normal prostatic tissue of the Copenhagen rats predominantly expressed proMMP-2 but not proMMP-9 whereas MMP-9 was only found in cancerous tissue. Elevated plasma MMP-9 values were demonstrated in rats with subcutaneous or orthotopic tumors. Animals with tumors and treated with the MMP inhibitor RO 28-2653 had both a lower tumor volume and a lower plasma MMP-9 concentration compared with controls. CONCLUSIONS: The determination of plasma MMP-9 in Dunning tumor rats is a useful tool to monitor the progression of prostate cancer and to assess the efficacy of drugs like MMP inhibitors or other treatment protocols.

Different mRNA and protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 in benign and malignant prostate tissue.

OBJECTIVE: The aim of this study was to assess the behavior of the matrix metalloproteinases (MMPs) 2 and 9 and the tissue inhibitor of metalloproteinases 1 (TIMP-1) in human prostate cancer. METHODS: mRNA and protein expression patterns of MMP-2, MMP-9, and TIMP-1 were studied in cancerous and noncancerous parts of 17 prostates removed by radical prostatectomy. Competitive RT-PCR, gelatin-substrate zymography, and ELISA techniques were used for quantification. RESULTS: On the mRNA level, MMP-2 expression was decreased and MMP-9, TIMP-1, the ratios of MMP-2 and MMP-9 to TIMP-1 were unchanged in cancerous tissue compared to the normal counterparts. On the protein level, expression of MMP-9 was significantly higher and TIMP-1 expression was significantly lower, MMP-2 was unchanged and the ratios of MMP-2 and MMP-9 to TIMP-1 were increased in tumor tissue. CONCLUSIONS: The higher concentration of MMP-9 as well as the increased ratios of MMP-2 and MMP-9 to TIMP-1 in malignant tissue prove the proteolytic dysbalance in prostate cancer, which does not seem to be associated with the stage and grade of the tumor. Comparison of mRNA and protein expression of MMP-2, MMP-9 and TIMP-1, respectively, did not show any significant relationships illustrating the necessity to study these components at both molecular levels.