Expression and activity of matrix metalloproteinases-2 and -9 in serum, core needle biopsies and tissue specimens of prostate cancer patients

Abstract

Prostate cancer is the most common cancer in men and second in the cancer-related frequency of mortality. Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis in various malignancies. MMP-2 and MMP-9 are capable of digesting collagen type IV. Numerous studies have demonstrated an association between increased MMP-2 and -9 expression and tumor progression in various tumors. In this study, the expression and activities of MMP-2 and -9 were assessed in serum probes and tumor tissue from core needle biopsies and radical prostatectomies of 97 patients. MMP-2 and -9 serum expression was analyzed in a subgroup of 31 patients. MMP-9 serum expression was significantly increased in tumor patients and correlated with tumor grade. In contrast, the MMP-9 tissue expression and activity revealed no significant correlations to tumor stage or grade. The MMP-2 activity, however, showed a positive correlation for MMP-2 with tumor stage. Increased activity was predominantly detected in advanced tumor stages. Immunohistochemical analysis of MMP-2 expression demonstrated a positive association with tumor grade in prostatectomy specimens. The relative expression rates in biopsies matched in 65% with those of the prostatectomies. Detection of MMP-2 in core needle biopsies seems not to be a helpful marker for diagnostic purposes.

The Use of Predictive or Prognostic Genetic Biomarkers in Endometrial and Other Hormone-Related Cancers: Justification for Extensive Candidate Gene Single Nucleotide Polymorphism Studies of the Matrix Metalloproteinase Family and their Inhibitors

“…As expected, all studies have reported an increase in the MMP-to-TIMP ratio in cancer samples and an association with unfavorable prognostic parameters (54,74,75). Regarding enzymatic activity, increased activity of MMP2, MMP7, and MMP9 proteins have been observed in hormone-related cancers and increased activity associated with a more aggressive phenotype (55,58,64,74,76), consistent with the hypothesized role of these enzymes in cancer progression and invasion.…”

“…However, expression studies done using immunohistochemistry and in situ hybridization on prostate cancer tissue have shown a decreasing gradient of MMP1 protein from normal adjacent prostate, prostate intraepithelial neoplasia, to prostate cancer tissue (52). Similarly, down-regulation of MMP2 mRNA was observed in prostate cancer compared with normal tissue in two studies (53,54), whereas increased expression of MMP2 protein has been reported in five studies (55)(56)(57)(58)(59). This suggests a discrepancy between MMP2 RNA and protein levels in prostate tumors.…”

Androgen Receptor and Invasion in Prostate Cancer

“…Among different MMPs, MMP-2 and MMP-9, called gelatinases, disrupt the basement membrane by cleaving type IV collagen. Many studies have shown that increased levels of MMP-2 or MMP-9 in the serum or tissue samples of prostate cancer patients are correlated with advanced stage (19)(20)(21)(22)(23)(24)(25)(26). Whereas MMP expression is regulated by growth factors and cytokines, as well as oncogenes (27)(28)(29), regulation of MMP-2 or MMP-9 activities by AR signaling in prostate cancer cells is controversial.…”

Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer

“…These findings were supported by a most recent independent report. 23 These parameters may be useful as a prognostic marker for human prostate cancer. Normalized Uzz its MMP-2 Figure 5 Relative activity of MMP-2 and -9 in serum samples.…”