Expression of Matrix Metalloproteinase-7 and Tissue Inhibitor of Metalloproteinase-1 in Human Prostate

Hashimoto, Kazuhito; Kihira, Yasunori; Matuo, Yuhsi; Usui, Tsuguru

doi:10.1097/00005392-199811000-00075

Cited by 28 publications

(36 citation statements)

References 17 publications

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“…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). Using both Northern analysis and in situ hybridization, Still and co-workers (27) linked increased MMP2 and TIMP2 to high tumor grade and advanced tumor stage of the disease.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading the structural support network for normal and malignant cells, promoting neoplastic cell invasion and metastasis. Tissue inhibitors of metalloproteinases (TIMPs) maintain connective tissue integrity by modulating MMP activity. Formalin-fixed paraffin-embedded tissue sections from 138 prostatic adenocarcinomas (PACs) were immunostained by a combined automated/manual method using monoclonal antibodies against MMP2 and TIMP2. Immunoreactivity was semiquantitatively scored based on stain intensity and distribution, and results were correlated with Gleason grade, pathologic stage, ploidy status, and disease recurrence. One hundred five of 138 (76%) and 113/138 (82%) PACs expressed MMP2 and TIMP2, respectively. Co-expression was observed in 94/138 (68%) of PACs (P ‫؍‬ .01), correlated with advanced tumor stage (P ‫؍‬ .05), and tended to be associated with disease recurrent cases (P ‫؍‬ .07). TIMP2 expression individually correlated with advanced tumor stage (P ‫؍‬ .04) and reached near significance with disease recurrence (P ‫؍‬ .06). MMP2 expression was also more frequent in recurrent PACs, although this value did not reach statistical significance (P ‫؍‬ .07). However, on multivariate analysis, only pathologic stage (P ‫؍‬ .009) and ploidy status (P ‫؍‬ .03) independently predicted disease recurrence. In conclusion, MMP2 and TIMP2 are co-expressed in a majority of PACs and correlate with prognostic variables. Interestingly, contrary to the previously documented anti-tumor effects of TIMPs, TIMP2 expression appears to have a tumorpromoting role in PACs and warrants further investigation. KEY WORDS: Immunohistochemistry, MMP, Prognosis, Prostate cancer, TIMP. Mod Pathol 2003;16(3):198 -205Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, degrade the basement membrane and extracellular matrix, facilitating cell migration, tumor invasion, and metastasis (1-5). There are at least 20 human MMPs, divided into the collagenases, gelatinases, stromelysins, and membrane-type MMPs (MT-MMPs; 1-5). Tissue inhibitors of metalloproteinases (TIMPs) are the major endogenous regulators of MMPs and consist of four homologous members (TIMP1-4; 6 -8). TIMPs are multifunctional proteins that inhibit cell invasion in vitro and tumorigenesis and metastasis in vivo (6). Although each TIMP appears capable of inhibiting several MMPs, these proteins exhibit preferential inhibitory capacity; for example, TIMPs1 and 2 selectively inhibit MMP9 and 2, respectively (9). Increased expression of MMPs has been associated with poor prognosis and shortened patient survival in a variety of malignancies including carcinomas of the esophagus (10), stomach (11), colon (12), breast (13), pancreas (14), lung (15), kidney (16), and ovary (17). TIMP expression has been associated with both tumor suppressor or antimetastatic effects and tumor-promoting effects in selected cancers (18 -20

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Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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“…2,56 -58 The role of MMPs and their inhibitors in cancer progression has been extensively studied. 7,22,59 In prostate cancer tissues, increasing expression of MMPs-1, 24,25 -2, 26 -32 -3, 24,29 -7 33 and -9 27,34 has been associated with increasing cancer burden. However, these studies did not distinguish between expression by stromal or epithelial cells that may interact to cause cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Characterization of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in prostate cancer cell lines

Daja

Niu

Zhao

et al. 2003

Prostate Cancer Prostatic Dis

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Stromal expression of some matrix metalloproteinases (MMPs) has been associated with increasing tumour burden in prostate cancer. We investigated the expression of mRNA (by RT-PCR) and protein (by zymography and western blotting) of MMPs and endogenous inhibitors (tissue inhibitors of metalloproteinases, TIMPs) in two parent epithelial prostate cancer cell lines and sublines of increasing invasive/metastatic potential. Expression of membrane type MMPs, MT1-MMP and MT3-MMP mRNA was higher in PC3-derived than in LNCaPderived lines, whereas MT2-MMP mRNA expression was higher in the LNCaPderived than in PC3-derived cell lines. Active MT1, MT2 and MT3-MMP protein levels were similar in all lines, but processed MT-MMPs, indicative of latent MMP activation, were increased in more aggressive sublines. Expression of MMP-1, MMP-13 and TIMP-1 was higher in the more aggressive sublines and may be implicated in invasive/metastatic ability. Regulation of MMP-1 and MMP-13 expression may offer important therapeutic options for treating patients with prostate cancer.

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“…There is considerable evidence supporting the involvement of MMPs and TIMPs in prostate cancer (Pajouh et al, 1991;Lokeshwar et al, 1993;Boag and Young, 1994;Wood et al, 1997;Hashimoto et al, 1998;Still et al, 2000;Srikantan et al, 2002;Trudel et al, 2003;Udayakumar et al, 2003;Zhao et al, 2003). However, research has focused almost entirely on the earlier discovered MMPs (MMP-2, -7 and -9) and TIMP-1 and -2; the more recently discovered MMPs have received little attention (Zhao et al, 2003).…”

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confidence: 99%

Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues

et al. 2005

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Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT -PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases of human prostate cancer and 23 benign prostate specimens. We found increased expression of MMP10, 15, 24, 25 and 26, urokinase plasminogen activator-receptor (uPAR) and plasminogen activator inhibitor-1 (PAI1), and the newly characterised serine proteases hepsin and matriptase-1 (MTSP1) in malignant tissue compared to benign prostate tissue. In contrast, there was significantly decreased expression of MMP2 and MMP23, maspin, and the protease inhibitors tissue inhibitor of metalloproteinase 3 (TIMP3), TIMP4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the cancer specimens. The expression of MMP15 and MMP26 correlated positively with Gleason score, whereas TIMP3, TIMP4 and RECK expression correlated negatively with Gleason score. The cellular localisation of the expression of the deregulated genes was evaluated using primary malignant epithelial and stromal cell cultures derived from radical prostatectomy specimens. MMP10 and 25, hepsin, MTSP1 and maspin showed predominantly epithelial expression, whereas TIMP 3 and 4, RECK, MMP2 and 23, uPAR and PAI1 were produced primarily by stromal cells. These data provide the first comprehensive and quantitative analysis of the expression and localisation of MMPs and their inhibitors in human prostate cancer, leading to the identification of several genes involved in proteolysis as potential prognostic indicators, in particular hepsin, MTSP1, MMP26, PAI1, uPAR, MMP15, TIMP3, TIMP4, maspin and RECK.

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Expression of Matrix Metalloproteinase-7 and Tissue Inhibitor of Metalloproteinase-1 in Human Prostate

Abstract: These results suggest that MMP-7 may play an important role for invasion and metastasis in prostate carcinomas, and the balance between MMP-7 and TIMP-1 expression may relate to an invasive ability of prostate carcinomas.

Cited by 28 publications

References 17 publications

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

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

Characterization of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in prostate cancer cell lines

Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues

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