The Experts below are selected from a list of 840 Experts worldwide ranked by ideXlab platform
Lynn M Matrisian - One of the best experts on this subject based on the ideXlab platform.
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Matrilysin (Matrix Metalloproteinase-7) Selects for Apoptosis-resistant Mammary
2013Co-Authors: Cells In Vivo, Howard C Crawford, Barbara Fingleton, Tracy Vargo-gogola, Lynn M MatrisianAbstract:Overexpression of the matrix metalloproteinase Matrilysin (matrix metalloproteinase-7) in the mouse mammary gland promotes mammary hyperplasia and accelerates the onset of oncogene-induced mammary tumors. In cell culture models, acute exposure of cells coexpressing Fas and Fas ligand (FasL) to Matrilysin induces apoptosis, whereas chronic exposure to Matrilysin selects for apoptosis-resistant cells. We now demonstrate that Matrilysin promotes resistance to apoptosis in vivo. Matrilysin expression increased apoptosis in the involuting mammary gland of mice that had undergone a single pregnancy and lactation cycle. Premature basement membrane disruption was detected in Matrilysin-expressing mice, which could account for the increase in apoptosis. However, multiparous mice, in which the involuting mammary epithelial cells have been repeatedly exposed to Matrilysin, show a significant decrease in apoptosis. Mammary tissue from multiparous Matrilysin-expressing mice showed decreased FasL expression, suggesting that loss of FasL is at least one mechanism of Matrilysin-induced resistance to apoptosis. We propose that Matrilysin promotes mammary tumor formation by enhancing the selection of cells that are resistant to apoptosis
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Matrilysin-dependent Elastolysis by Human Macrophages
2003Co-Authors: Sergey Filippov, Lynn M Matrisian, Ingrid Caras, Richard Murray, Harold A. Chapman, Steven D. Shapiro, Stephen J. WeissAbstract:Human macrophages found in juxtaposition to fragmented elastin in vivo express the elastolytic matrix metalloproteinases (MMPs) progelatinase B, prometalloelastase, and proMatrilysin. Though MMPs can degrade a range of extracellular matrix components, increasing evidence suggests that preferred targets in vivo include nonmatrix substrates such as chemokines and growth factors. Hence, the means by which MMPs participate in elastin turnover remain undefined as does the identity of the elastolysins. Herein, human macrophage cultures have been established that express a complement of elastolytic proteinases similar, if not identical, to that found in vivo. Under plasminogen-free conditions, macrophages preferentially use metalloelastase to mediate elastolysis via a process that deposits active enzyme on elastin surfaces. By contrast, in the presence of plasminogen, human macrophages up-regulate proteolysis 10-fold by processing proMatrilysin to an active elastolysin via a urokinase-type plasminogen activator-dependent pathway. Matrilysin-deficient human macrophages fail to mediate an elastolytic response despite the continued expression of gelatinase B and metalloelastase. Thus, acting in concert with cosecreted cysteine proteinases whose activities are constrained to sites of macrophage-elastin contact (Punturieri, A., S. Filippov, E. Allen, I. Caras, R. Murray, V. Reddy, and S.J. Weiss. 2000. J. Exp. Med. 192:789–799), Matrilysin confers macrophages with their most potent MMP-dependent elastolytic system.
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synergistic cooperation between the ap 1 and lef 1 transcription factors in activation of the Matrilysin promoter by the src oncogene implications in cellular invasion
2003Co-Authors: Christine Rivat, Lynn M Matrisian, Howard C Crawford, Nathalie Le Floch, Michele Sabbah, Isabelle Teyrol, Gerard Redeuilh, Erik Bruyneel, Marc Mareel, Christian GespachAbstract:SPECIFIC AIMThe matrix metalloprotease Matrilysin (MMP-7) is overexpressed in several human solid tumors and 90% adenomas from familial adenomatous polyposis patients, suggesting its critical role ...
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Matrilysin matrix metalloproteinase 7 selects for apoptosis resistant mammary cells in vivo
2002Co-Authors: Tracy Vargogogola, Barbara Fingleton, Howard C Crawford, Lynn M MatrisianAbstract:Overexpression of the matrix metalloproteinase Matrilysin (matrix metalloproteinase-7) in the mouse mammary gland promotes mammary hyperplasia and accelerates the onset of oncogene-induced mammary tumors. In cell culture models, acute exposure of cells coexpressing Fas and Fas ligand (FasL) to Matrilysin induces apoptosis, whereas chronic exposure to Matrilysin selects for apoptosis-resistant cells. We now demonstrate that Matrilysin promotes resistance to apoptosis in vivo. Matrilysin expression increased apoptosis in the involuting mammary gland of mice that had undergone a single pregnancy and lactation cycle. Premature basement membrane disruption was detected in Matrilysin-expressing mice, which could account for the increase in apoptosis. However, multiparous mice, in which the involuting mammary epithelial cells have been repeatedly exposed to Matrilysin, show a significant decrease in apoptosis. Mammary tissue from multiparous Matrilysin-expressing mice showed decreased FasL expression, suggesting that loss of FasL is at least one mechanism of Matrilysin-induced resistance to apoptosis. We propose that Matrilysin promotes mammary tumor formation by enhancing the selection of cells that are resistant to apoptosis.
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Matrilysin matrix metalloproteinase 7 expression in ulcerative colitis related tumorigenesis
2002Co-Authors: Ken J Newell, Lynn M Matrisian, David K DrimanAbstract:Matrilysin (matrix metalloproteinase-7) plays a part in the initiation and growth of colorectal tumors; expression of this protein has been implicated in tumor invasion and metastasis. To date, Matrilysin expression in ulcerative colitis (UC)-associated tumorigenesis has not been studied. The aim of this study was to assess the immunohistochemical expression of Matrilysin at different stages of UC-associated neoplasia. Paraffin-embedded specimens from 25 patients with UC without dysplasia, UC-related low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and UC-associated carcinoma as well as four colon biopsy samples with no abnormality were examined using an anti-human Matrilysin monoclonal antibody and standard immunoperoxidase techniques. Matrilysin expression was recorded as the number of positive cases and the percentage of positive crypts as follows: normal: none of four; negative results for dysplasia: seven of 12 ( 50%). The results indicated an apparent switch from focal expression of Matrilysin in UC-related low-grade dysplasia to widespread expression in high-grade dysplasia and invasive cancer, mimicking the pattern of expression in sporadic colorectal cancer. Although the sample size is small and further investigation therefore is required, the results suggest the possible role of anti-matrix metalloproteinase therapy in reducing the risk of progression from LGD to cancer in patients with ulcerative colitis. Published 2002 Wiley-Liss, Inc.
William C Parks - One of the best experts on this subject based on the ideXlab platform.
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Epithelial and Mesenchymal Cell Biology Tissue Inhibitor of Metalloproteinase-1 Moderates Airway Re-Epithelialization by Regulating Matrilysin Activity
2015Co-Authors: Peter Chen, John K Mcguire, Robert C Hackman, Kyoung Hee Kim, Roy A Black, Kurt Poindexter, Wei Yan, Phillip Liu, Ann J. Chen, William C ParksAbstract:Obliterative bronchiolitis (OB) is the histopathologi-cal finding in chronic lung allograft rejection. Mount-ing evidence suggests that epithelial damage drives the development of airway fibrosis in OB. Tissue in-hibitor of metalloproteinase (TIMP)-1 expression in-creases in lung allografts and is associated with the onset of allograft rejection. Furthermore, in a mouse model of OB, airway obliteration is reduced in TIMP-1-deficient mice. Matrilysin (matrix metallprotein-ase-7) is essential for airway epithelial repair and is required for the re-epithelialization of airway wounds by facilitating cell migration; therefore, the goal of this study was to determine whether TIMP-1 inhibits re-epithelialization throughMatrilysin. We found that TIMP-1 and Matrilysin co-localized in the epitheliu
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egress by generating chemokine gradients
2013Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:Matrix metalloproteinase-7 (Matrilysin) controls neutrophi
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Matrix metalloproteinase-7 (Matrilysin) controls neutrophil egress by generating chemokine gradients
2013Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:(MMP7)] is induced by mucosal injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7 �/ � mice to acute colon injury. When Matrilysin expression was increasing, 73 % of wild-type mice died, whereas only 32 % of Mmp7 �/ � mice succumbed. Although re-epithelialization was delayed in Mmp7 �/ � mice, overall injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7 �/ � mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7 �/ � mice. The levels of neutrophil chemokines, keratinocyte-derived chemokine and MIP-2, increased in the colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that Matrilysin mediates beneficial and deleterious effects in response to injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead t
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Bacterial Exposure Induces and Activates Matrilysin in Mucosal
2013Co-Authors: Epithelial Cells, Carole L Wilson, Lora V Hooper, Jeffrey I Gordon, Scott J Hultgren, A S. López-boado, William C ParksAbstract:Abstract. Matrilysin, a matrix metalloproteinase, is expressed and secreted lumenally by intact mucosal and glandular epithelia throughout the body, suggesting that its regulation and function are shared among tissues. Because Matrilysin is produced in Paneth cells of the murine small intestine, where it participates in innate host defense by activation of prodefensins, we speculated that its expression would be influenced by bacterial exposure. Indeed, acute infection (10–90 min) of human colon, bladder, and lung carcinoma cells, primary human tracheal epithelial cells, and human tracheal explants with type 1–piliated Escherichia coli mediated a marked (25–50-fold) and sustained (�24 h) induction of Matrilysin production. In addition, bacterial infection resulted in activation of the zymogen form of the enzyme, which was selectively released at the apical surface. Induction of Matrilysin was mediated by a soluble, non-LPS bacterial factor and correlated with the release of defensin-like bacteriocidal activity. Bacteria did not induce Matrilysin in other cell types, and expression of other metalloproteinases by epithelial cells was not affected by bacteria. Matrilysin was not detected in germ-free mice, but the enzyme was induced after colonization with Bacteroides thetaiotaomicron. These findings indicate that bacterial exposure is a potent and physiologically relevant signal regulating Matrilysin expression in epithelial cells. Key words: metalloproteinase • bacteria • adhesin • defensin • host defens
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matrix metalloproteinase 7 Matrilysin controls neutrophil egress by generating chemokine gradients
2008Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:Matrilysin [matrix metalloproteinase 7 (MMP7)] is induced by mucosal injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7(-/-) mice to acute colon injury. When Matrilysin expression was increasing, 73% of wild-type mice died, whereas only 32% of Mmp7(-/-) mice succumbed. Although re-epithelialization was delayed in Mmp7(-/-) mice, overall injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7(-/-) mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7(-/-) mice. The levels of neutrophil chemokines, keratinocyte-derived chemokine and MIP-2, increased in the colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that Matrilysin mediates beneficial and deleterious effects in response to injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead to tissue damage.
Hiroyuki Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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insulin like growth factor i receptor blockade reduces the invasiveness of gastrointestinal cancers via blocking production of Matrilysin
2009Co-Authors: Yasushi Adachi, Hiroyuki Yamamoto, Arisa Imsumran, Kohzoh Imai, Yoshiaki Arimura, Yongfen Min, Wenhua Piao, Yu Wang, Choon Taek Lee, David P CarboneAbstract:Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of gastrointestinal (GI) cancers. We have previously shown significant therapeutic activity for recombinant adenoviruses expressing dominant-negative insulin-like growth factor-I receptor (IGF-IR/dn), including suppression of tumor invasion. In this study, we sought to evaluate the mechanism of inhibition of invasion and the relationship between IGF-IR and matrix metalloproteinase (MMP) activity in GI carcinomas. We analyzed the role of IGF-IR on invasion in three GI cancer cell lines, colorectal adenocarcinoma, HT29; pancreatic adenocarcinoma, BxPC3 and gastric adenocarcinoma, MKN45, using a modified Boyden chamber method and subcutaneous xenografts in nude mice. The impact of IGF-IR signaling on the expression of MMPs and the effects of blockade of Matrilysin or IGF-IR on invasiveness were assessed using recombinant adenoviruses, a tyrosine kinase inhibitor NVP-AEW541 and antisense Matrilysin. Invasive subcutaneous tumors expressed several MMPs. IGF-IR/dn reduced the expression of these MMPs but especially Matrilysin (MMP-7). Insulin-like growth factor (IGF) stimulated secretion of Matrilysin and IGF-IR/dn blocked IGF-mediated Matrilysin induction in three GI cancers. Both IGF-IR/ dn and inhibition of Matrilysin reduced in vitro invasion to the same degree. NVP-AEW541 also reduced cancer cell invasion both in vitro and in murine xenograft tumors via suppression of Matrilysin. Thus, blockade of IGF-IR is involved in the suppression of cancer cell invasion through downregulation of Matrilysin. Strategies of targeting IGF-IR may have significant therapeutic utility to prevent invasion and progression of human GI carcinomas.
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role of matrix metalloproteinase 7 Matrilysin in human cancer invasion apoptosis growth and angiogenesis
2006Co-Authors: Hiroyuki Yamamoto, Yasushi Adachi, Yumiko Maruyama, Yasuhisa ShinomuraAbstract:Matrix metalloproteinase (MMP)-7, also known as Matrilysin, is a "minimal domain MMP" that exhibits proteolytic activity against components of the extracellular matrix (ECM). Matrilysin is frequently overexpressed in human cancer tissues and is associated with cancer progression. Tumorigenesis is a multistep process involving cell growth, invasion, metastasis, and angiogenesis. Matrilysin has been shown to play important roles not only in degradation of ECM proteins, but also in the regulation of several biochemical processes such as activation, degradation, and shedding of non-ECM proteins. This minire-view provides a summary of the current literature on the roles of Matrilysin in tumorigenesis with a focus on the roles of modifications of non-ECM proteins by Matrilysin and other related MMPs in tumorigenesis. Proteolysis of insulin-like growth factor binding protein by Matrilysin results in increased bioavailability of insulin-like growth factors and enhanced cellular proliferation. Matrilysin has also been implicated in the ectodomain shedding of several cell surface molecules. Heparin-binding epidermal growth factor precursor (proHB-EGF) is cleaved by Matrilysin into mature HB-EGF, which promotes cellular proliferation. Membrane-bound Fas ligand (FasL) is cleaved into soluble FasL, which increases apoptosis of cells adjacent to tumor cells. E-cadherin is converted to soluble E-cadherin to promote invasion. Tumor necrosis factor (TNF)-alpha precursor is cleaved to release soluble TNF-alpha to increase apoptosis. We propose that these Matrilysin-mediated pathways provide the necessary and logical mechanisms to promote cancer progression.
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tumour Matrilysin expression predicts metastatic potential of stage i pt1 colon and rectal cancers
2005Co-Authors: Sei Kurokawa, Hiroyuki Yamamoto, Yasushi Adachi, Masao Hosokawa, Yoshiaki Arimura, Yasuhisa Shinomura, T Endo, T Sato, Toshihiro Suga, Kohzoh ImaiAbstract:Background and aims: Nodal metastases are indisputable determinants of prognosis for colon and rectal cancer. Using classical histological criteria, many attempts to predict nodal metastasis have failed, preventing the adequate management of stage I (pT1) cancer. We investigated the role of tumour Matrilysin in predicting metastatic potential, and discuss its potential use in individualising treatment of pT1 colon and rectal cancer. Methods: The gene signature associated with nodal metastasis was investigated by cDNA array in 24 colon and rectal cancers. We studied 494 colon and rectal cancer patients to identify risk factors for nodal metastasis and evaluated the potential to predict nodal metastasis by either the logistic regression model or the Bayesian neural network model with built-in Matrilysin. We then inferred possible causality of nodal metastasis from structural equation modelling. Results: cDNA array revealed that Matrilysin was maximally upregulated in the metastasis signature identified. Tumour Matrilysin expression emerged as a stage independent risk factor for nodal metastasis, resulting in a similar predictive performance in receiver operating characteristic curve analysis in the two models. A Bayesian approach called automatic relevance determination identified Matrilysin as one of the most relevant predictors examined. Structural equation modelling suggested possible direct causality between Matrilysin and nodal metastasis. Conclusions: We have provided evidence that tumour Matrilysin expression is a promising biomarker predicting nodal metastasis of colon and rectal cancer. Analysis of tumour Matrilysin expression would help clinicians achieve the goal of individualised cancer treatment based on the metastatic potential of pT1 colon and rectal cancer.
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association of Matrilysin 2 mmp 26 expression with tumor progression and activation of mmp 9 in esophageal squamous cell carcinoma
2004Co-Authors: Hiroyuki Yamamoto, Akravit Vinitketkumnuen, Yasushi Adachi, Hiroaki Taniguchi, Tamaki Hirata, Nobuki Miyamoto, Katsuhiko Nosho, Arisa Imsumran, Masahiro Fujita, Masao HosokawaAbstract:Expression of Matrilysin-2, matrix metalloproteinase (MMP)-26, has been implicated in the progression of several types of human cancer. Matrilysin-2 has been reported to be a physiological and pathological activator of pro-MMP-9. The aim of this study was to examine Matrilysin-2 expression and determine whether it is correlated with progression of human esophageal squamous cell carcinoma (ESCC). Semi-quantitative reverse transcriptase-polymerase chain reaction, immunohistochemical analysis, zymography and an in vitro invasion assay were performed. Matrilysin-2 mRNA expression was undetectable or only faintly detected in non-tumor tissues, but its overexpression was detected in 24 of the 50 ESCC tissues. Matrilysin-2 overexpression was significantly correlated with depth of invasion, lymph node metastasis and an advance in pathological tumor node metastasis (pTNM) stage. Sections with immunostaining signals in >10% of carcinoma cells at the invasive front, which were observed in 46 of 100 cases, were judged to be positive for Matrilysin-2 expression. Matrilysin-2 expression was significantly correlated with depth of invasion, lymph node and distant metastasis, advance in pTNM stage and recurrence. Expression of Matrilysin-2 was significantly correlated with nuclear beta-catenin expression and MMP-9 expression. Patients with Matrilysin-2-positive cancer had significantly shorter overall and disease-free survival periods than did those with Matrilysin-2-negative cancer. Matrilysin-2 expression retained its significant predictive value for overall and disease-free survival in multivariate analysis. Moreover, patients with concomitant expression of Matrilysin-2 and MMP-9 had the worst prognosis. Zymography revealed that Matrilysin-2 expression was significantly correlated with expression of active MMP-9 in ESCC tissues. Matrilysin-2-transfected TE-1 ESCC cells showed active MMP-9 activity and were more invasive in vitro compared with mock-transfected TE-1 cells. The results of this study suggest that Matrilysin-2, the expression of which is closely correlated with nuclear beta-catenin expression and active MMP-9 activity, plays a key role in the progression of ESCC.
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expression of ets related transcriptional factor e1af is associated with tumor progression and over expression of Matrilysin in human gastric cancer
2003Co-Authors: Hiroyuki Yamamoto, Yasushi Adachi, Hiroaki Taniguchi, Katsuhiko Nosho, Yongfen Min, Shina Horiuchi, Kohzoh ImaiAbstract:Expression of E1AF/PEA3 (ETV4), an ets family transcriptional factor, has been implicated in tumor progression through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and to determine whether it is correlated with progression of, and/or MMP expression in, human gastric cancer. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we analyzed 100 gastric cancer tissues for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other two members of the PEA3 subfamily, and Ets-1 and Ets-2 was also analyzed. The results were correlated with clinicopathological characteristics and MMP expression. Immunohistochemical analysis and an in vitro invasion assay were also performed. E1AF mRNA expression was detected in 64% of the 100 gastric cancer tissues, but was undetectable or only faintly detected in adjacent non-tumor tissues. E1AF expression was significantly correlated with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advance in pathological tumor-node-metastasis stage and recurrence. Patients with E1AF-positive tumors had significantly shorter overall and disease-free survival periods than did those with E1AF-negative tumors (P < 0.0001 and P < 0.0001, respectively). E1AF expression retained its significant predictive value for overall and disease-free survival in multivariate analysis that included conventional clinicopathological factors (P = 0.0082 and P = 0.0096, respectively). Among the MMPs analyzed, expression of Matrilysin (MMP-7) was significantly correlated with E1AF expression. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of Matrilysin was often co-localized. Antisense E1AF-transfected MKN45 gastric cancer cells expressed reduced levels of Matrilysin and were less invasive in vitro than mock-transfected MKN45 cells. The results of this study suggest that E1AF, the expression of which is closely correlated with the expression of Matrilysin, plays a key role in the progression of gastric cancer.
John K Mcguire - One of the best experts on this subject based on the ideXlab platform.
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Epithelial and Mesenchymal Cell Biology Tissue Inhibitor of Metalloproteinase-1 Moderates Airway Re-Epithelialization by Regulating Matrilysin Activity
2015Co-Authors: Peter Chen, John K Mcguire, Robert C Hackman, Kyoung Hee Kim, Roy A Black, Kurt Poindexter, Wei Yan, Phillip Liu, Ann J. Chen, William C ParksAbstract:Obliterative bronchiolitis (OB) is the histopathologi-cal finding in chronic lung allograft rejection. Mount-ing evidence suggests that epithelial damage drives the development of airway fibrosis in OB. Tissue in-hibitor of metalloproteinase (TIMP)-1 expression in-creases in lung allografts and is associated with the onset of allograft rejection. Furthermore, in a mouse model of OB, airway obliteration is reduced in TIMP-1-deficient mice. Matrilysin (matrix metallprotein-ase-7) is essential for airway epithelial repair and is required for the re-epithelialization of airway wounds by facilitating cell migration; therefore, the goal of this study was to determine whether TIMP-1 inhibits re-epithelialization throughMatrilysin. We found that TIMP-1 and Matrilysin co-localized in the epitheliu
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Matrilysin mmp 7 catalytic activity regulates β catenin localization and signaling activation in lung epithelial cells
2014Co-Authors: Cliff Rims, John K McguireAbstract:ABSTRACTMatrix metalloproteinase-7 (Matrilysin, MMP-7) expression is increased in epithelium by bacterial infection, inflammation, fibrosis, and in a myriad of carcinomas. It functions to degrade extracellular matrix and other pericellular substrates including the adherens junction protein E-cadherin to promote wound healing and tissue remodeling. β-catenin functions as both a structural component of adherens junctions and as an intracellular signaling molecule. To assess if Matrilysin-mediated disassembly of adherens junctions regulates β-catenin function, we assessed effects of Matrilysin catalytic activity on β-catenin localization and signaling activity in A549 cells and in bleomycin-induced lung injury in mice. We determined that Matrilysin activity releases β-catenin from the cell membrane after which it is degraded in the cytosol. However, in the presence of a β-catenin stabilizing Wnt signal, β-catenin accumulated in the cytosol and activated a β-catenin luciferase promoter. Furthermore, β-catenin...
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egress by generating chemokine gradients
2013Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:Matrix metalloproteinase-7 (Matrilysin) controls neutrophi
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Matrix metalloproteinase-7 (Matrilysin) controls neutrophil egress by generating chemokine gradients
2013Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:(MMP7)] is induced by mucosal injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7 �/ � mice to acute colon injury. When Matrilysin expression was increasing, 73 % of wild-type mice died, whereas only 32 % of Mmp7 �/ � mice succumbed. Although re-epithelialization was delayed in Mmp7 �/ � mice, overall injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7 �/ � mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7 �/ � mice. The levels of neutrophil chemokines, keratinocyte-derived chemokine and MIP-2, increased in the colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that Matrilysin mediates beneficial and deleterious effects in response to injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead t
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Matrilysin mmp 7 inhibition of bmp 7 induced renal tubular branching morphogenesis suggests a role in the pathogenesis of human renal dysplasia
2012Co-Authors: John K Mcguire, Helen Liapis, Susanna Harjubaker, Cliff Rims, Joong Hyuk SheenAbstract:Congenital renal dysplasia (RD) is a severe form of congenital renal malformation characterized by disruption of normal renal development with cyst formation, reduced or absent nephrons, and impaired renal growth. The authors previously identified that Matrilysin (matrix metalloproteinase-7) was overexpressed in a microarray gene expression analysis of human RD compared to normal control kidneys. They now find that active Matrilysin gene transcription and protein synthesis occur within dysplastic tubules and epithelial cells lining cysts in human RD by RT-PCR and immunohistochemistry. Similar staining patterns were seen in obstructed kidneys of pouch opossums that show histological features similar to that of human RD. In vitro, Matrilysin inhibits formation of branching structures in mIMCD-3 cells stimulated by bone morphogenetic protein-7 (BMP-7) but does not inhibit hepatocyte growth factor-stimulated branching. BMP-7 signaling is essential for normal kidney development, and overexpression of catalytically active Matrilysin in human embryonic kidney 293 cells reduces endogenous BMP-7 protein levels and inhibits phosphorylation of BMP-7 SMAD signaling intermediates. These findings suggest that Matrilysin expression in RD may be an injury response that disrupts normal nephrogenesis by impairing BMP-7 signaling.
Kohzoh Imai - One of the best experts on this subject based on the ideXlab platform.
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insulin like growth factor i receptor blockade reduces the invasiveness of gastrointestinal cancers via blocking production of Matrilysin
2009Co-Authors: Yasushi Adachi, Hiroyuki Yamamoto, Arisa Imsumran, Kohzoh Imai, Yoshiaki Arimura, Yongfen Min, Wenhua Piao, Yu Wang, Choon Taek Lee, David P CarboneAbstract:Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of gastrointestinal (GI) cancers. We have previously shown significant therapeutic activity for recombinant adenoviruses expressing dominant-negative insulin-like growth factor-I receptor (IGF-IR/dn), including suppression of tumor invasion. In this study, we sought to evaluate the mechanism of inhibition of invasion and the relationship between IGF-IR and matrix metalloproteinase (MMP) activity in GI carcinomas. We analyzed the role of IGF-IR on invasion in three GI cancer cell lines, colorectal adenocarcinoma, HT29; pancreatic adenocarcinoma, BxPC3 and gastric adenocarcinoma, MKN45, using a modified Boyden chamber method and subcutaneous xenografts in nude mice. The impact of IGF-IR signaling on the expression of MMPs and the effects of blockade of Matrilysin or IGF-IR on invasiveness were assessed using recombinant adenoviruses, a tyrosine kinase inhibitor NVP-AEW541 and antisense Matrilysin. Invasive subcutaneous tumors expressed several MMPs. IGF-IR/dn reduced the expression of these MMPs but especially Matrilysin (MMP-7). Insulin-like growth factor (IGF) stimulated secretion of Matrilysin and IGF-IR/dn blocked IGF-mediated Matrilysin induction in three GI cancers. Both IGF-IR/ dn and inhibition of Matrilysin reduced in vitro invasion to the same degree. NVP-AEW541 also reduced cancer cell invasion both in vitro and in murine xenograft tumors via suppression of Matrilysin. Thus, blockade of IGF-IR is involved in the suppression of cancer cell invasion through downregulation of Matrilysin. Strategies of targeting IGF-IR may have significant therapeutic utility to prevent invasion and progression of human GI carcinomas.
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tumour Matrilysin expression predicts metastatic potential of stage i pt1 colon and rectal cancers
2005Co-Authors: Sei Kurokawa, Hiroyuki Yamamoto, Yasushi Adachi, Masao Hosokawa, Yoshiaki Arimura, Yasuhisa Shinomura, T Endo, T Sato, Toshihiro Suga, Kohzoh ImaiAbstract:Background and aims: Nodal metastases are indisputable determinants of prognosis for colon and rectal cancer. Using classical histological criteria, many attempts to predict nodal metastasis have failed, preventing the adequate management of stage I (pT1) cancer. We investigated the role of tumour Matrilysin in predicting metastatic potential, and discuss its potential use in individualising treatment of pT1 colon and rectal cancer. Methods: The gene signature associated with nodal metastasis was investigated by cDNA array in 24 colon and rectal cancers. We studied 494 colon and rectal cancer patients to identify risk factors for nodal metastasis and evaluated the potential to predict nodal metastasis by either the logistic regression model or the Bayesian neural network model with built-in Matrilysin. We then inferred possible causality of nodal metastasis from structural equation modelling. Results: cDNA array revealed that Matrilysin was maximally upregulated in the metastasis signature identified. Tumour Matrilysin expression emerged as a stage independent risk factor for nodal metastasis, resulting in a similar predictive performance in receiver operating characteristic curve analysis in the two models. A Bayesian approach called automatic relevance determination identified Matrilysin as one of the most relevant predictors examined. Structural equation modelling suggested possible direct causality between Matrilysin and nodal metastasis. Conclusions: We have provided evidence that tumour Matrilysin expression is a promising biomarker predicting nodal metastasis of colon and rectal cancer. Analysis of tumour Matrilysin expression would help clinicians achieve the goal of individualised cancer treatment based on the metastatic potential of pT1 colon and rectal cancer.
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expression of ets related transcriptional factor e1af is associated with tumor progression and over expression of Matrilysin in human gastric cancer
2003Co-Authors: Hiroyuki Yamamoto, Yasushi Adachi, Hiroaki Taniguchi, Katsuhiko Nosho, Yongfen Min, Shina Horiuchi, Kohzoh ImaiAbstract:Expression of E1AF/PEA3 (ETV4), an ets family transcriptional factor, has been implicated in tumor progression through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and to determine whether it is correlated with progression of, and/or MMP expression in, human gastric cancer. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we analyzed 100 gastric cancer tissues for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other two members of the PEA3 subfamily, and Ets-1 and Ets-2 was also analyzed. The results were correlated with clinicopathological characteristics and MMP expression. Immunohistochemical analysis and an in vitro invasion assay were also performed. E1AF mRNA expression was detected in 64% of the 100 gastric cancer tissues, but was undetectable or only faintly detected in adjacent non-tumor tissues. E1AF expression was significantly correlated with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advance in pathological tumor-node-metastasis stage and recurrence. Patients with E1AF-positive tumors had significantly shorter overall and disease-free survival periods than did those with E1AF-negative tumors (P < 0.0001 and P < 0.0001, respectively). E1AF expression retained its significant predictive value for overall and disease-free survival in multivariate analysis that included conventional clinicopathological factors (P = 0.0082 and P = 0.0096, respectively). Among the MMPs analyzed, expression of Matrilysin (MMP-7) was significantly correlated with E1AF expression. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of Matrilysin was often co-localized. Antisense E1AF-transfected MKN45 gastric cancer cells expressed reduced levels of Matrilysin and were less invasive in vitro than mock-transfected MKN45 cells. The results of this study suggest that E1AF, the expression of which is closely correlated with the expression of Matrilysin, plays a key role in the progression of gastric cancer.
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association of ets related transcriptional factor e1af expression with tumour progression and overexpression of mmp 1 and Matrilysin in human colorectal cancer
2003Co-Authors: Shina Horiuchi, Hiroyuki Yamamoto, Yasushi Adachi, Fumio Itoh, Yongfen Min, Kohzoh ImaiAbstract:Expression of E1AF/PEA3 (ETV4), an ets family transcription factor, has been implicated in the invasive potential of several cancer cell lines through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and to determine whether it is correlated with progression of, and/or MMP expression in, human colorectal cancer. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), 100 colorectal cancer tissues were analysed for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other two members of the PEA3 subfamily, and Ets-1 and Ets-2 was also analysed. The results were correlated with clinicopathological characteristics and MMP expression. Immunohistochemical analysis and an in vitro invasion assay were also performed. E1AF mRNA expression was detected in 62% of the 100 colorectal cancer tissues, but was undetectable or only faintly detected in adjacent non-tumour tissues. E1AF mRNA was detected in all of the ten liver metastases from colorectal cancers. E1AF expression correlated significantly with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advance in pathological tumour-node-metastasis stage, and recurrence. Patients with E1AF-positive tumours had significantly shorter overall and disease-free survival periods than did those with E1AF-negative tumours (p < 0.0001 and p < 0.0001, respectively). E1AF expression retained its significant predictive value for overall and disease-free survival in multivariate analysis that included conventional clinicopathological factors (p = 0.0066 and p = 0.0109, respectively). Among the MMPs analysed, expression of MMP-1 and Matrilysin correlated significantly with E1AF expression. In contrast, expression of ER81 and ERM did not correlate with clinicopathological characteristics or the expression of these MMPs. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of MMP-1 and Matrilysin and nuclear beta-catenin expression were often co-localized. Antisense E1AF-transfected HT-29 colon cancer cells expressed reduced levels of MMP-1 and Matrilysin and were less invasive in vitro than neo-transfected HT-29 cells. The results of this study suggest that E1AF, the expression of which is closely correlated with the expression of MMP-1 and Matrilysin, plays a key role in the progression of colorectal cancer.
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the expression of matrix metalloproteinase Matrilysin indicates the degree of inflammation in ulcerative colitis
2003Co-Authors: Keiki Matsuno, Hiroyuki Yamamoto, Yasushi Adachi, Fumio Itoh, Yoshiaki Arimura, Takao Endo, Akira Goto, Kohzoh ImaiAbstract:Any alteration in the synthesis and breakdown of the extracellular matrix is important in tissue remodeling during inflammation and wound healing. The degradation of the extracellular matrix components is regulated by a cascade of matrix metalloproteinases (MMPs). The present study attempted to assess the relationship between MMPs and the degree of inflammation in ulcerative colitis. Methods: The expression of MMPs, including MMP-1, -2, -3, -7 (Matrilysin), and -9, and that of their inhibitors (tissue inhibitor of metalloproteinases [TIMP]-1 and -2) were analyzed immunohistochemically by using 52 formalin-fixed and paraffin-embedded specimens from patients with ulcerative colitis who had undergone a biopsy or surgery. Results: It was observed that MMP-1, -2, and -9, and the TIMPs were expressed in stromal cells, MMP-3 was expressed in both the epithelial cells and stromal components, and Matrilysin was expressed only in the epithelial cells on the edge of ulcers. The expression of the MMPs was increased compared with that of the TIMPs. The frequency of Matrilysin expression was increased corresponding to the severity of the inflammation. Matrilysin was also expressed in epithelial cells with dysplasia and cancer. Conclusions: Matrilysin expression could be an important marker of activity and could be used for the prediction of subsequent transformation in patients with ulcerative colitis.