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Jon S. Friedland - One of the best experts on this subject based on the ideXlab platform.
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Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis
'Frontiers Media SA', 2018Co-Authors: Sara Brilha, Deborah L. W. Chong, Akif A. Khawaja, Catherine W. M. Ong, Naomi J. Guppy, Joanna C. Porter, Jon S. FriedlandAbstract:Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix Metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular Matrix (ECM) modulates M. tuberculosis-driven Matrix Metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen Matrix. Matrix Metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of Metalloproteinases. Decreased Matrix Metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen Matrix showed an increase in Matrix Metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen Matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was Matrix Metalloproteinase-dependent, since it was blocked by the Matrix Metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate Matrix Metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB
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Table_1_Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.PDF
2018Co-Authors: Sara Brilha, Deborah L. W. Chong, Akif A. Khawaja, Catherine W. M. Ong, Naomi J. Guppy, Joanna C. Porter, Jon S. FriedlandAbstract:Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix Metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular Matrix (ECM) modulates M. tuberculosis-driven Matrix Metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen Matrix. Matrix Metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of Metalloproteinases. Decreased Matrix Metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen Matrix showed an increase in Matrix Metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen Matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was Matrix Metalloproteinase-dependent, since it was blocked by the Matrix Metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate Matrix Metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB.
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Image_2_Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.PDF
2018Co-Authors: Sara Brilha, Deborah L. W. Chong, Akif A. Khawaja, Catherine W. M. Ong, Naomi J. Guppy, Joanna C. Porter, Jon S. FriedlandAbstract:Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix Metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular Matrix (ECM) modulates M. tuberculosis-driven Matrix Metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen Matrix. Matrix Metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of Metalloproteinases. Decreased Matrix Metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen Matrix showed an increase in Matrix Metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen Matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was Matrix Metalloproteinase-dependent, since it was blocked by the Matrix Metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate Matrix Metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB.
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multinucleate giant cells release functionally unopposed Matrix Metalloproteinase 9 in vitro and in vivo
The Journal of Infectious Diseases, 2007Co-Authors: Xing Wu Zhu, Nicholas M Price, Robert H Gilman, Sixto Recarvarren, Jon S. FriedlandAbstract:Multinucleated giant cells (MGCs) are characteristic of granulomatous inflammation. Matrix Metalloproteinase (MMP)-9, the major monocyte-derived Matrix Metalloproteinase, is key in inflammatory tissue damage. At 72 h, MGCs secrete 153 +/- 2.5 ng/mL MMP-9, compared with 115 +/- 3.8 ng/mL during macrophage differentiation (P<.05). In contrast, the level of MGC secretion-specific tissue inhibitor, tissue inhibitor of Metalloproteinase (TIMP)-1, is lower (P<.05). Mature MGCs secrete constitutively greater concentrations of MMP-9 than do monocytes or macrophages (P<.05). MGCs in tuberculous lymph-node biopsy samples express high MMP-9 levels adjacent to areas of necrosis, whereas TIMP-1 is not detected. Thus, MGCs are potentially important sources of MMP-9 secretion and may contribute to inflammatory tissue damage in human tuberculosis.
Roberto Romero - One of the best experts on this subject based on the ideXlab platform.
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the relationship between amniotic fluid Matrix Metalloproteinase 8 and funisitis
American Journal of Obstetrics and Gynecology, 2001Co-Authors: Joong Shin Park, Jeong Bin Moon, Sooyoung Oh, Bo Hyun Yoon, Roberto Romero, Eun-mi KoAbstract:Abstract Objective: The fetal inflammatory response syndrome is a multisystem disorder associated with impending preterm delivery and adverse neonatal outcome. Inflammation of the umbilical cord—funisitis— is the histologic counterpart of fetal inflammatory response syndrome and has been associated with an increased risk for the development of cerebral palsy. Neutrophils found in the amniotic cavity are of fetal origin. Therefore, neutrophil secretory products may be an index of the fetal inflammatory response syndrome. To test this hypothesis, we examined the relationship between levels of amniotic fluid Matrix Metalloproteinase-8 and funisitis. Study Design: The relationship between the presence of funisitis and concentrations of amniotic fluid Matrix Metalloproteinase-8 was examined in 255 consecutive patients who delivered preterm singleton neonates (gestational age, Results: Funisitis was present in 23% (59/255) of cases. Patients with funisitis had a significantly higher median concentration of amniotic fluid Matrix Metalloproteinase-8 than those without funisitis (median, 433.7 ng/mL [range, 1.5-3836.8 ng/mL] vs median, 1.9 ng/mL [range, P Conclusions: There is a strong association between increased levels of amniotic fluid Matrix Metalloproteinase-8 and funisitis. We propose that determination of amniotic fluid Matrix Metalloproteinase-8 concentrations may assist the assessment of the fetal inflammatory status, thereby eliminating the need for fetal blood sampling. (Am J Obstet Gynecol 2001;185:1156-61.)
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an elevated amniotic fluid Matrix Metalloproteinase 8 level at the time of mid trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery
American Journal of Obstetrics and Gynecology, 2001Co-Authors: Bo Hyun Yoon, Roberto Romero, Joong Shin Park, Soonsup Shim, Sooyeon Han, Jong Kwan JunAbstract:Abstract Objective: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid Matrix Metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. Study Design: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid Matrix Metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix Metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. Results: The median amniotic fluid Matrix Metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (Matrix Metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, P P P Conclusions: Elevated mid-trimester concentrations of amniotic fluid Matrix Metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery ( 23 ng/mL is a powerful predictor of spontaneous preterm delivery (
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a role for Matrix Metalloproteinase 9 in spontaneous rupture of the fetal membranes
American Journal of Obstetrics and Gynecology, 1998Co-Authors: Neil Athayde, Roberto Romero, Samuel S Edwin, Ricardo Gomez, Eli Maymon, Percy Pacora, Ramkumar MenonAbstract:Abstract Objectives: Preterm premature rupture of fetal membranes is responsible for 30% to 40% of preterm deliveries. Fetal membranes are composed primarily of collagen. Matrix Metalloproteinases are enzymes capable of degrading extracellular Matrix macromolecules, including collagens. Expression of Matrix Metalloproteinase-9 (gelatinase B, 92 kd) and its tissue inhibitor (tissue inhibitor of Metalloproteinase-1) has been localized in amnion and chorion. The objective of this study was to determine whether rupture of fetal membranes and intrauterine infection are associated with changes in the expression of Matrix Metalloproteinase-9 and tissue inhibitor of Metalloproteinase-1. Study Design: Two hundred one women in the following categories had amniotic fluid retrieved: (1) preterm labor and intact membranes in the presence (n = 42) or absence (n = 21) of microbial invasion of the amniotic cavity, (2) preterm premature rupture of the membranes with (n = 29) or without (n = 23) microbial invasion of the amniotic cavity, and (3) term gestation with intact membranes (n = 50) or with premature rupture of the membranes (n = 40). Women in groups 1 and 2 were matched for gestational age at amniocentesis. Microbial invasion of the amniotic cavity was defined by a positive amniotic fluid culture for micro-organisms. Matrix Metalloproteinase-9 and tissue inhibitor of Metalloproteinase-1 were measured with use of sensitive and specific immunoassays that were validated for amniotic fluid. Results: Spontaneous rupture of membranes at term is associated with a significant increase in the amniotic fluid concentrations of Matrix Metalloproteinase-9 (premature rupture of membranes, no labor: median 3.9 ng/mL, range 2.7 to 11.1 ng/mL vs no premature rupture of membranes, no labor: median P P = .06). Women with microbial invasion of the amniotic cavity had higher median Matrix Metalloproteinase-9 concentrations than did those without microbial invasion regardless of membrane status (preterm labor: 54.5 ng/mL, range P P Conclusion: Our data support a role for Matrix Metalloproteinase-9 in the mechanisms responsible for membrane rupture in term and preterm gestations. (Am J Obstet Gynecol 1998;179:1248-53.)
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 Matrix Metalloproteinase 7 selects for apoptosis resistant mammary cells in vivo
Cancer Research, 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
Molecular Carcinogenesis, 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.
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structure and expression of the human gene for the Matrix Metalloproteinase matrilysin
Journal of Biological Chemistry, 1994Co-Authors: Mireille Gaire, Susan Mcdonnell, Zenaida V Magbanua, Leslie Mcneil, David H Lovett, Lynn M MatrisianAbstract:Matrilysin, a member of the Matrix Metalloproteinase family, is structurally different from the other Matrix Metalloproteinases by virtue of the absence of a conserved COOH-terminal protein domain. In addition, matrilysin mRNA is regulated in a specific and distinct manner in normal and malignant tissues. Analysis of the genomic structure of the human matrilysin gene revealed that the organization of the first five exons is highly conserved among the different members of the Matrix Metalloproteinase family, but that matrilysin contains an atypical sixth exon. The promoter region of the matrilysin gene has several features that are conserved among several other Matrix Metalloproteinase family members, including the presence of TATA, AP-1, and PEA3 elements. Comparison of the expression of the human matrilysin promoter with rat stromelysin promoter/chloramphenicol acetyltransferase constructs in HeLa cells revealed that constructs containing AP-1 and PEA3 elements respond similarly to epidermal growth factor and tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) induction, but that the addition of upstream stromelysin sequences results in an increased transcriptional activity not observed with upstream matrilysin sequences. The similarities and differences observed between the promoters of matrilysin and the other Metalloproteinases may provide insights into the molecular mechanisms that regulate the expression of this family of enzymes as a whole and the factors that distinguish the expression patterns of individual family members.
Joong Shin Park - One of the best experts on this subject based on the ideXlab platform.
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the relationship between amniotic fluid Matrix Metalloproteinase 8 and funisitis
American Journal of Obstetrics and Gynecology, 2001Co-Authors: Joong Shin Park, Jeong Bin Moon, Sooyoung Oh, Bo Hyun Yoon, Roberto Romero, Eun-mi KoAbstract:Abstract Objective: The fetal inflammatory response syndrome is a multisystem disorder associated with impending preterm delivery and adverse neonatal outcome. Inflammation of the umbilical cord—funisitis— is the histologic counterpart of fetal inflammatory response syndrome and has been associated with an increased risk for the development of cerebral palsy. Neutrophils found in the amniotic cavity are of fetal origin. Therefore, neutrophil secretory products may be an index of the fetal inflammatory response syndrome. To test this hypothesis, we examined the relationship between levels of amniotic fluid Matrix Metalloproteinase-8 and funisitis. Study Design: The relationship between the presence of funisitis and concentrations of amniotic fluid Matrix Metalloproteinase-8 was examined in 255 consecutive patients who delivered preterm singleton neonates (gestational age, Results: Funisitis was present in 23% (59/255) of cases. Patients with funisitis had a significantly higher median concentration of amniotic fluid Matrix Metalloproteinase-8 than those without funisitis (median, 433.7 ng/mL [range, 1.5-3836.8 ng/mL] vs median, 1.9 ng/mL [range, P Conclusions: There is a strong association between increased levels of amniotic fluid Matrix Metalloproteinase-8 and funisitis. We propose that determination of amniotic fluid Matrix Metalloproteinase-8 concentrations may assist the assessment of the fetal inflammatory status, thereby eliminating the need for fetal blood sampling. (Am J Obstet Gynecol 2001;185:1156-61.)
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an elevated amniotic fluid Matrix Metalloproteinase 8 level at the time of mid trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery
American Journal of Obstetrics and Gynecology, 2001Co-Authors: Bo Hyun Yoon, Roberto Romero, Joong Shin Park, Soonsup Shim, Sooyeon Han, Jong Kwan JunAbstract:Abstract Objective: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid Matrix Metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. Study Design: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid Matrix Metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix Metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. Results: The median amniotic fluid Matrix Metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (Matrix Metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, P P P Conclusions: Elevated mid-trimester concentrations of amniotic fluid Matrix Metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery ( 23 ng/mL is a powerful predictor of spontaneous preterm delivery (
Peter Shamamian - One of the best experts on this subject based on the ideXlab platform.
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increased membrane type 1 Matrix Metalloproteinase expression from adenoma to colon cancer a possible mechanism of neoplastic progression
Diseases of The Colon & Rectum, 2002Co-Authors: Sandeep Malhotra, Elliot Newman, David Eisenberg, John V Scholes, Rosemary Wieczorek, Paolo Mignatti, Peter ShamamianAbstract:PURPOSE: Membrane type 1 Matrix Metalloproteinase is a membrane-associated Matrix Metalloproteinase central to the degradation of basement membrane components via the activation of Matrix Metalloproteinase-2. Although membrane type 1 Matrix Metalloproteinase is overexpressed in invasive colon cancer, its expression in colonic polyps and carcinoma in situ has not been defined. In addition, the association of membrane type 1 Matrix Metalloproteinase expression by a primary tumor and recurrence of colon cancers has not been examined. METHODS: Immunoperoxidase staining was performed on randomly selected specimens containing adenoma (n = 17), carcinoma in situ (n = 9), or metastatic colon carcinoma (n = 8) with mouse monoclonal antibody to human membrane type 1 Matrix Metalloproteinase. Similar staining was also performed on randomly selected node-negative colon cancers that recurred within five years of resection (n = 17), matched for age, gender, stage, grade, and vascular, lymphatic, and perineural invasion, and node-negative colon cancers that did not recur within five years of resection (n = 17). Staining for membrane type 1 Matrix Metalloproteinase was graded. Mean scores for the groups were compared by Wilcoxon test. RESULTS: We found a progressive and significant increase in the mean score of membrane type 1 Matrix Metalloproteinase from normal mucosa to adenoma (P < 0.001), carcinoma in situ (P < 0.006), and invasive cancer (P < 0.009). However, there was no difference in membrane type 1 Matrix Metalloproteinase expression between the recurrent and nonrecurrent groups of node-negative colon cancer (P = not significant). CONCLUSIONS: These data suggest that membrane type 1 Matrix Metalloproteinase expression increases with progression from normal mucosa to invasive adenocarcinoma; however, it cannot be used as a prognostic indicator on which adjuvant therapy is based in node-negative colon cancer because of its failure to predict recurrence in this patient group.