Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma.

Sakamoto, Yosuke; Mafune, Ken–ichi; Mori, Miki; Shiraishi, Takeshi; Imamura, Hiroshi; Takayama, Takuya; Makuuchi, M

doi:10.3892/ijo.17.2.237

Cited by 54 publications

(66 citation statements)

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“…[43][44][45][46][47] In this study, we were unable to document progressive changes of MMPs as hepatocellular carcinoma progress from low to high grade except a significantly higher level of expression of MMP-7 in metastatic hepatocellular carcinoma. MMP-7, also know as matrilysin, is the smallest MMP.…”

Section: Discussionmentioning

confidence: 87%

Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma

et al. 2006

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Molecular markers can provide additional information to traditional histomorphological evaluation for the assessment of tumor progression and predicting the likelihood of invasion and metastasis in various types of malignancies. We studied the association of E-cadherin, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinase with the progression and metastasis of hepatocellular carcinoma. Tissue microarray including six normal livers, 14 cirrhotic livers, 39 macroregenerative nodules, 16 dysplastic nodules, 22 grade I hepatocellular carcinomas, 43 grade II hepatocellular carcinomas, seven grade III hepatocellular carcinomas, and 10 metastatic hepatocellular carcinomas were stained immunohistochemically with antibodies against MMPs -1, -2, -3, -7, -9, tissue inhibitors of metalloproteinase-1, -2, -3, and E-cadherin. The intensities of staining were scored manually by two pathologists and verified by the Chromavision Automated Cellular Imaging System. Compared with normal liver, cirrhotic liver had significantly lower E-cadherin and tissue inhibitors of metalloproteinase-1 but higher MMP-1 and -7, which suggest a more favorable environment for tumor invasion and metastasis. Grade I and grade II hepatocellular carcinomas demonstrated high E-cadherin and decreased MMP-3 and -9, which may explain the rarity of extrahepatic metastasis in low-grade hepatocellular carcinomas despite the high circulatory volume of the liver. The histological progression from dysplastic nodule to well-differentiated hepatocellular carcinoma and to less differentiated tumors was associated with a gradual decrease in tissue expression of E-cadherin, tissue inhibitors of metalloproteinase-2 and -3. Metastatic hepatocellular carcinomas showed significantly lower level of tissue inhibitors of metalloproteinase-1, -2, -3 but higher level of MMP-7. These data suggest that tissue expression of E-cadherin, certain MMPs, and tissue inhibitors of metalloproteinases could be useful markers to predict the progression and metastasis of hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 87%

Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma

et al. 2006

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“…43 Increased expression levels of MMP-2 have been associated with unfavorable outcome also in gastric cancer, 44 in urothelial cancer 45 and in early stage non-small cell lung cancer. 46 Overexpression of MMP-9 is related to well differentiated hepatocellular carcinoma 47 and to recurrence in early non-small cell lung carcinoma. 48 MT1-MMP expression in tumor tissue is associated with invasiveness and poor prognosis of laryngeal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

High expression levels of collagenase‐1 and stromelysin‐1 correlate with shorter disease‐free survival in human metastatic melanoma

Nikkola

Vihinen

Vlaykova

et al. 2001

Intl Journal of Cancer

119

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Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor-induced angiogenesis. We studied the expression of collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and collagenase-3 (MMP-13) in 70 melanoma metastases obtained from 56 patients treated with combined chemoimmunotherapy. The patients were divided into 2 groups using a cut-off point of 0% for MMP-1 expression and 20% for MMP-3 expression. We found that patients with MMP-1 positive metastases (n ‫؍‬ 38) had significantly shorter disease-free survival compared to patients with MMP-1 negative metastases (n ‫؍‬ 18) (median 11.2 vs. 17.0 months, p ‫؍‬ 0.0383). The disease-free survival of patients with high levels of MMP-3 expression in their metastases (>20% positive tumor cells, n ‫؍‬ 14) was also significantly shorter compared to patients with lower levels of expression (n ‫؍‬ 42) (median 5.1 vs. 14.0 months, p ‫؍‬ 0.0294). The expression of MMP-13 did not correlate to survival parameters. We also found that the presence of melanin, a pigment produced by melanocytes, correlated with high expression levels of MMP-1 (p ‫؍‬ 0.0002), MMP-3 (p < 0.0001) and MMP-13 (p ‫؍‬ 0.0009). The high expression levels of MMP-13 were also associated with the presence of visceral metastases (p ‫؍‬ 0.0284). Our findings suggest that MMP-1 and -3 may have a special role in melanoma metastasis formation and thus they could be used to measure the biological activity of the disease. © 2002 Wiley-Liss, Inc. Key words: MMP-1; MMP-3; MMP-13; melanin; metastatic melanoma; disease-free survivalMatrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases that can degrade essentially all extracellular matrix components. At present, the human MMP gene family contains 21 members that can be divided into subgroups of collagenases, gelatinases, stromelysins, membrane-type MMPs (MT-MMPs) and novel MMPs according to their substrate specificity and primary structure. 1,2 There are specific tissue inhibitors of metalloproteinases (TIMPs) that can inhibit the activity of MMPs. The balance between MMPs and their inhibitors is essential in many physiological conditions as well as in pathological conditions such as rheumatoid arthritis, atherosclerosis, tumor invasion, metastasis and tumor-induced neovascularization. 3,4 Members of the collagenase subgroup, i.e., collagenase-1 (MMP-1), collagenase-2 (MMP-8) and collagenase-3 (MMP-13), are only neutral proteinases capable of degrading native fibrillar collagens of types I, II, III and V. After initial cleavage by collagenases followed by denaturation the fibrillar collagens are further degraded by gelatinases. MMP-13 has exceptionally wide substrate specificity compared to other MMPs. In addition to native fibrillar collagens it degrades type IV, X and XIV collagens, tenascin, fibronectin and the aggrecan core protein. 2 Stromelysin-1 (MMP-3) was one of the first proteinases found to be associated with cancer. 5 MMP-3 ...

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“…MMP-26 did not cleave pro-MMP-2, another gelatinase, indicating that pro-MMP-9 activation by MMP-26 is highly selective. MMP-9 is a powerful enzyme, and is considered to be an important contributor to the processes of invasion, metastasis, and angiogenesis in various tumors (11)(12)(13)(14)(32)(33)(34)(35)(36).…”

Section: Reduction Of Invasiveness Of Mmp-26 Antisense Stable Transfementioning

confidence: 99%

“…Another member of the MMP family considered to be an important contributor to the processes of invasion, metastasis, and angiogenesis exhibited by tumor cells is gelatinase B (MMP-9) (11)(12)(13)(14). have demonstrated that MMP-26 is able to cleave MMP-9, and here we examine the possibility that MMP-26 facilitates tumor cell invasion through the activation of pro-MMP-9.…”

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confidence: 99%

Activation of Pro-gelatinase B by Endometase/Matrilysin-2 Promotes Invasion of Human Prostate Cancer Cells

Zhao

Xiao

Newcomer

et al. 2003

Journal of Biological Chemistry

116

140

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This work has explored a putative biochemical mechanism by which endometase/matrilysin-2/matrix metalloproteinase-26 (MMP-26) may promote human prostate cancer cell invasion. Here, we showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular tissues. The role of MMP-26 in prostate cancer progression is unknown. MMP-26 was capable of activating pro-MMP-9 by cleavage at the Ala 93 -Met 94 site of the prepro-enzyme. This activation proceeded in a time-and dose-dependent manner, facilitating the efficient cleavage of fibronectin by MMP-9. The activated MMP-9 products generated by MMP-26 appeared more stable than those cleaved by MMP-7 under the conditions tested. During the initial phases of carcinoma cell invasion, as tumor cells begin to spread and infiltrate into the surrounding normal tissues, these cells must first degrade the basement membrane and other elements of the extracellular matrix (ECM), 1 including type IV collagen, laminin, and fibronectin (FN) (1). Multiple protease families, including the matrix metalloproteinases (MMPs), serine proteases, and cysteine proteases, are suspected of contributing to the invasive and metastatic abilities of a variety of malignant tumors (2-5), but the specific biochemical mechanisms that facilitate these invasive behaviors remain elusive.More than 23 human MMPs, and numerous homologues from other species, have been reported (5), and matrix metalloproteinase-26 (MMP-26)/endometase/matrilysin-2 is a novel member of this enzyme family that was recently cloned and characterized by our group (6) and others (7-9). MMP-26 mRNA is primarily expressed in epithelial cancers, such as lung, breast, endometrial, and prostate carcinomas, in their corresponding cell lines (6 -9), and in a very limited number of normal adult tissues, such as the uterus (6, 8), placenta (7,8), and kidney (9). Recently, we have found that the levels of MMP-26 gene and protein expression are higher in a malignant choriocarcinoma cell line (JEG-3) than in normal human cytotrophoblast cells (10). Our preliminary studies indicate that expression of MMP-26 may be correlated with the malignant transformation of human prostate and breast epithelial cells. The specific expression of MMP-26 in malignant tumors and the proteolytic activity of this enzyme against multiple components of the ECM, including fibronectin, type IV collagen, vitronectin, gelatins, and fibrinogen, as well as non-ECM proteins such as insulin-like growth factor-binding protein 1 and ␣1-protease inhibitor (6 -9), indicate that MMP-26 may possess an important function in tumor progression.Another member of the MMP family considered to be an important contributor to the processes of invasion, metastasis, and angiogenesis exhibited by tumor cells is gelatinase B (MMP-9) (11-14). Uría and López-Otín (8) have demonstrated that MMP-26 is able to cleave MMP-9, and here we examine the possibility that MMP...

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Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma.

Cited by 54 publications

References 0 publications

Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma

Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma

High expression levels of collagenase‐1 and stromelysin‐1 correlate with shorter disease‐free survival in human metastatic melanoma

Activation of Pro-gelatinase B by Endometase/Matrilysin-2 Promotes Invasion of Human Prostate Cancer Cells

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