Expression of metalloproteinase genes in human prostate cancer

Abstract

Twenty-five surgical specimens of malignant human prostate, 3 lymph nodes with metastatic prostate carcinoma, 11 normal human prostates, as well as 3 human prostate cell lines (DU-145, PC3 and LNCaP) were examined for the expression of the human matrix metalloproteinase-7 gene (MMP-7) from the human collagenase family (originally called PUMP-1 for putative metalloproteinase-1) [Quantin et al. (1989) Biochemistry 28:5327-5334; Muller et al. (1988) Biochem J 253:187-192; Matrisian and Bowden (1990) Semin Cancer Biol 1:107-115]. Northern blots were prepared using total RNA extracted from 18 prostate adenocarcinomas, 2 lymph nodes with metastatic prostate carcinoma and 11 normal human prostates. When the northern blots were hybridized with a 32P-labeled MMP-7 cDNA probe, a 1.2-kb mRNA was detected in 14 out of 18 prostate adenocarcinomas, 1 out of 2 metastatic lymph nodes, and 3 out of 11 normal prostates. The 3 human prostate cell lines did not show any evidence of the MMP-7 transcript. In situ hybridization was conducted to localize the MMP-7 mRNA to individual cells using a 35S-labeled MMP-7 cRNA. In situ hybridization was carried out on snap-frozen tissue sections of 7 prostate adenocarcinomas and 3 lymph nodes containing metastatic prostate adenocarcinoma using the same tissues previously probed by northern analysis as well as new samples. In situ hybridization revealed that the MMP-7 gene was expressed in the epithelial cells of primary prostate adenocarcinoma as well as in invasive and metastatic cells. MMP-7 expression was also seen focally in some dysplastic glands but not in stroma. Additional northern blot analysis was performed using probes to human type-IV collagenase, type-I collagenase and stromelysin I in human prostate adenocarcinoma as well as normal prostate tissue. Our results indicated that 6 out of 10 adenocarcinoma samples and none of the 4 normal samples were positive for type-IV collagenase transcripts. Tissue samples were also examined for the expression of type-I collagenase (9 adenocarcinomas and 4 normal) and stromelysin I (13 adenocarcinomas) by northern analysis. None of the tissues was found to express the transcripts of interest at detectable levels. These data suggest that certain metalloproteinases are present in prostatic adenocarcinoma and may play a role in invasion and metastasis.

Prognostic Significance of Matrix Metalloproteinase 2 and Tissue Inhibitor of Metalloproteinase 2 Expression in Prostate Cancer

“…Cancer outcome studies have also shown that increased expression of MMPs is associated with shortened patient survival (10,12,46). Aberrant expression of MMPs in prostate cancer was first described using in situ hybridization in 1991 (31). MMP7 expression has been linked to prostate cancer pathologic stage and incidence of metastasis (33).…”

A phase II trial of marimastat in advanced pancreatic cancer

“…MMPs have an important physiological role in embryonic development (Brenner et al, 1989), bone remodelling (Delaisse and Vaes, 1992) and wound healing (Wolf et al, 1992), and a major role in pathological processes including rheumatoid arthritis (Harris, 1990) and cancer invasion and metastasis (Liotta and Stetler-Stevenson, 1991). MMP overexpression has been reported in carcinomas of the ovary (Campo et al, 1992), prostate (Pajouh et al, 1991) and lung (Brown et al, 1993) and MMP activity correlated with malignant potential in gastric (Nomura et al, 1995) and colorectal (Mori et al, 1995;Porte et al, 1995) cancer.…”

Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ-cultured prostate tissue: Levels of collagenolytic and gelatinolytic MMPs are low, variable and different in fresh tissue versus organ-cultured tissue

“…In contrast to the expression of these gelatinolytic enzymes (with type IV collagenolytic activity), there is little evidence for elaboration of enzymes which can degrade interstitial connective tissue. Pajouh et al (1991) reported that mRNA for MMP-1 (interstitial collagenase) was not detectable in either normal or malignant prostate specimens. MMP-1 immunoreactivity was detected in plasma of prostate cancer patients, but the amount detected was not significantly different from amount present in normal volunteers (Jung et al, 1997).…”