Metalloproteinase 2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas. (2004 Apr)
metalloproteinase 2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas . matrix metalloproteinases compose a family of enzymes involved in degradation of the extracellular matrix . tumor cells must penetrate the basement membrane and traverse the extracellular matrix in order to invade surrounding structures and metastasize to distant sites . gelatinases , particularly gelatinase A ( matrix metalloproteinase 2 ) , demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ squamous cell carcinoma lesions . matrix metalloproteinase 2 overexpression has been correlated with tumor invasiveness and metastasis in a wide variety of cancer types , including squamous cell carcinoma arising on mucous membranes . however , correlation between matrix metalloproteinase 2 overexpression and the spread and prognosis of cutaneous squamous cell carcinoma has not been characterized in the literature at present . In this study , we used immunohistochemical techniques to examine the expression of matrix metalloproteinase 2 in 10 actinic keratosis , 15 in situ , 13 invasive , 13 primary ( with documented metastatic disease ) , 11 metastatic , and 8 recurrent squamous cell carcinoma cases . We found that while the average staining intensity ( scale 0 3 , 3 being strongest ) of actinic keratosis and in situ lesions was not statistically significant ( 0 . 87 1 . 3 and 0 . 75 1 . 4 , respectively ) , the average staining intensity of invasive squamous cell carcinomas ( 1 . 6 …

Lung transplant ischemia reperfusion injury : metalloprotease inhibition down regulates exposure of type V collagen , growth related oncogene induced … (2008 Mar)
Lung transplant ischemia reperfusion injury : metalloprotease inhibition down regulates exposure of type V collagen , growth related oncogene induced neutrophil chemotaxis , and tumor necrosis factor alpha expression . background : immunity to type V collagen col ( V ) contributes to lung transplant rejection . matrix metalloproteases ( MMPs ) , which are induced by transplant related ischemia reperfusion injury ( IRI ) , could expose col ( V ) and regulate local IRI induced inflammation . methods : To test the hypothesis that MMPs induce col ( V ) exposure and inflammation , wistar kyoto rats were treated with the MMP inhibitor , COL 3 , before inducing lung IRI without transplantation , and in parallel studies , wistar kyoto lung donor and recipients were treated with COL 3 pre and postisograft lung transplantation . results : ischemia reperfusion injury induced growth related oncogene / CINC 1 dependent neutrophil influx , and up regulated tumor necrosis factor alpha . MMP2 and MMP9 , induced at 4 and 24 hr after IRI , respectively , were associated with detection of antigenic col ( V ) in bronchoalveolar lavage and lung interstitium because of MMP mediated matrix degradation . MMP inhibitor treatment significantly reduced polymorphonuclear leukocytes , growth related oncogene / CINC 1 , and tumor necrosis factor alpha ; abrogated MMP 9 expression ; and resulted in lower levels of antigenic col ( V ) in bronchoalveolar lavage . In the lung transplant model , inhibiting MMPs in …

Human eosinophils release matrix metalloproteinase 9 on stimulation with TNF alpha. (1999 Dec)
human eosinophils release matrix metalloproteinase 9 on stimulation with TNF alpha . background : The eosinophil is a prominent cell in allergic lung inflammation and is exposed to a range of cytokines , including TNF alpha , at the site of allergen challenge . matrix metalloproteinases ( MMPs ) and tissue inhibitors of matrix metalloproteinases ( timps ) produced by inflammatory cells are thought to play a crucial role in interstitial matrix turnover and tissue remodeling in acute and chronic lung diseases . In addition , protein kinase C is known to be important in MMP 9 expression and secretion . objective : We investigated the regulation of eosinophil derived MMP 9 and TIMP proteins by TNF alpha . methods : using RT PCR and gelatin zymography , we investigated the ability of human eosinophils to produce and secrete active MMP 9 on stimulation with TNF alpha . We also studied the production of TIMP 1 and TIMP 2 in eosinophils by using western blotting . results : The gelatinolytic activity of MMP 9 in unstimulated eosinophils was low , but it increased by 95 after TNF alpha stimulation . This increase was regulated at both the transcriptional and translational levels . The transcription inhibitor actinomycin D , the nuclear factor kappab ( nfkappab ) inhibitor N CBZ Leu Leu Leu AL , the protein synthesis inhibitor cycloheximide , and the protein kinase C inhibitor H7 significantly decreased MMP 9 activity in TNF alpha treated cells . TIMP 1 and …

Selective regulation of metalloproteinase inhibitor ( TIMP 1 ) by oncostatin M in fibroblasts in culture. (1993 Jul)
selective regulation of metalloproteinase inhibitor ( TIMP 1 ) by oncostatin M in fibroblasts in culture . tissue inhibitor of metalloproteinases ( TIMP 1 ) is a potent inhibitor of activated matrix metalloproteinases ( MMP ) such as collagenase , stromelysin , and gelatinase , and thus helps to control extracellular matrix metabolism and deposition by connective tissue cells . since various cytokines and growth factors can modify the production of MMP and TIMP 1 , we explored the action of oncostatin M ( OM ) , a unique lymphocyte and monocyte derived cytokine , on expression of these proteins . We examined the regulation of TIMP 1 expression in cultured human fibroblasts by cytokines including OM , IL 6 , leukemia inhibitory factor ( LIF ) , and IL 1 alpha . When used at levels of 5 to 50 ng / ml , OM , IL 6 , LIF , and IL 1 alpha elevated the TIMP 1 expression at the RNA level in fibroblasts of lung or synovial origin . interestingly , OM stimulation resulted in highest levels of TIMP 1 RNA and protein synthesis . however , unlike IL 1 alpha , the cytokines OM , IL 6 , and LIF did not induce MMP or PGE2 release . OM also enhanced TIMP 1 mRNA levels in the h2981 lung carcinoma and hepg2 hepatoma cell lines . The results suggest that OM as well as IL 6 and LIF , other cytokines acting through similar receptor …

Eosinophils as a source of matrix metalloproteinase 9 in asthmatic airway inflammation. (1997 Apr)
eosinophils as a source of matrix metalloproteinase 9 in asthmatic airway inflammation . bronchial asthma is characterized by eosinophil infiltration and tissue remodeling . matrix metalloproteinases ( MMPs ) are thought to play critical roles by degradating interstitial matrices in a wide range of lung diseases associated with reorganization of the airway architecture . To investigate whether MMPs are involved in the pathologic processes of bronchial asthma , we examined MMP expression in asthmatic subjects . In situ hybridization revealed abundant expression of MMP 9 ( gelatinase B ) mRNA in biopsy specimens from asthmatic subjects ( n 5 ) , with an average positive cell distribution of 117 . 8 / 41 . 1 ( mean / SEM ) / mm2 . In contrast , sparse expression of the mRNA ( 10 . 8 / 4 . 8 / mm2 ) was observed in specimens from normal subjects ( n 4 ) . The vast majority of cells expressing the mRNA were eosinophils in asthmatic tissues ( 92 . 2 / 1 . 2 ) . MMP 9 protein , which was confined to the submucosal cells in the normal subjects , was not abundantly expressed in inflammatory cells , but there was positive reactivity for MMP 9 protein in the extracellular matrix . immunoelectron microscopic analysis showed sparse immunolocalization of MMP 9 in the perinuclear spaces of eosinophils , but not in the granules . these findings suggest the overexpression of MMP 9 by eosinophils in bronchial tissues …

Collagenase 3 ( matrix metalloproteinase 13 ) expression is induced in oral mucosal epithelium during chronic inflammation. (1998 Jul)
collagenase 3 ( matrix metalloproteinase 13 ) expression is induced in oral mucosal epithelium during chronic inflammation . increased proliferation of mucosal epithelium during inflammation is associated with degradation of subepithelial connective tissue matrix and local invasion of the epithelial cells . Here we have studied , whether collagenase 3 ( MMP 13 ) , a collagenolytic matrix metalloproteinase with an exceptionally wide substrate specificity , is expressed in the epithelium of chronically inflamed mucosa . examination of human gingival tissue sections from subjects with chronic adult periodontitis with in situ hybridization revealed marked expression of MMP 13 in basal cells of some epithelial rete ridges expanding into connective tissue . immunohistochemical staining demonstrated that these cells also expressed strongly laminin 5 , suggesting that they are actively migrating cells . A strong signal for MMP 13 mRNA was occasionally also noted in the suprabasal epithelial cells facing the gingival pocket , whereas no collagenase 1 ( MMP 1 ) mRNA was detected in any areas of the epithelium . MMP 13 expression was also detected in fibroblast like cells associated with collagen fibers of the inflamed subepithelial connective tissue . In organ culture of human oral mucosa , MMP 13 mRNA expression was observed in epithelial cells growing into connective tissue of the specimens . regulation of MMP 13 expression was examined in cultured normal nonkeratinizing epithelial cells isolated from porcine periodontal ligament . In these cells , MMP 13 expression at the mRNA and protein level was potently …

Proteolytic activation of corneal matrix metalloproteinase by pseudomonas aeruginosa elastase. (1993 Feb)
proteolytic activation of corneal matrix metalloproteinase by pseudomonas aeruginosa elastase . purified pseudomonas aeruginosa elastase cleaved a 65 kDa gelatinase inactive proenzyme form of matrix metalloproteinase ( MMP 2 ) from human corneal fibroblasts into a biologically active fragment with an approximate molecular mass of 58 kDa . however , purified pseudomonal alkaline protease did not cleave MMP 2 appreciably . since activated MMP 2 is known to degrade native type IV , V and VII collagens , all components of the corneal basement membrane or stroma , our results suggest a new role for pseudomonal elastase in the pathogenesis of corneal infection , inflammation and ulceration .

Differential temporal expression of matrix metalloproteinases after spinal cord injury : relationship to revascularization and wound healing. (2003 Sep)
differential temporal expression of matrix metalloproteinases after spinal cord injury : relationship to revascularization and wound healing . object : matrix metalloproteinases ( MMPs ) , particularly MMP 9 / gelatinase B , promote early inflammation and barrier disruption after spinal cord injury ( SCI ) . early blockade of MMPs after injury provides neuroprotection and improves motor outcome . there is recent evidence , however , that MMP 9 and MMP 2 / gelatinase A participate in later wound healing in the injured cord . The authors therefore examined the activity of these gelatinases during revascularization and glial scar formation in the contused murine spinal cord . methods : gelatinase activity was evaluated using gelatin zymography 24 hours after a mild , moderate , or severe contusion injury . The active form of MMP 2 was not detected , whereas MMP 9 activity was evident in all SCI groups and rose with increasing injury severity . The temporal expression of gelatinases was then examined using gelatin zymography after a moderate SCI . The active form of MMP 9 was most prominent at 1 day , extended through the early period of revascularization , and returned to control by 14 days . The active form of MMP 2 appeared at 7 days postinjury and remained elevated compared with that documented in sham treated mice for at least 21 days . increased MMP 2 activity coincided with both revascularization and glial scar formation . using in situ zymography , gelatinolytic activity …

Clinical significance of gelatinases in septic arthritis of native and replaced knees. (2004 Nov)
clinical significance of gelatinases in septic arthritis of native and replaced knees . We hypothesized that more gelatinases appear in effusions of septic arthritis than aseptic arthritis . This study examined the laboratory variables of inflammation and the levels of gelatinase A and B ( matrix metalloproteinases 2 and 9 ) in 75 effusions from the knees of 37 patients with inflammatory arthritis and compared them with effusions of septic and aseptic arthritis . gelatin zymography revealed that the levels of the latent matrix metalloproteinase 9 were higher in 24 effusions of septic arthritis than in 51 effusions of aseptic arthritis . The latent matrix metalloproteinase 9 levels of septic arthritis also correlated with the neutrophil counts in effusions . significantly more activated matrix metalloproteinases 2 and 9 appeared in effusions of septic arthritis in native and replaced knees than in effusions of aseptic arthritis . A high matrix metalloproteinase 9 level and the appearance of activated matrix metalloproteinases 2 and 9 may distinguish septic from aseptic arthritis , even in cases with a low neutrophil count in the replaced knee . joint aspiration may not only reduce the bacteria counts , endotoxins , and proinflammatory cytokines , but also decrease the amount of matrix metalloproteinases in effusions that attack the extracellular matrix of native and artificial joints .

Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors. (2004 Jun)
modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors . Over expression of matrix metalloproteinases by lung fibroblasts has been blamed for much of the tissue destruction associated with airway inflammation . because cyclic AMP is known to regulate fibroblast proliferation , as well as cytokine and extracellular matrix protein production , the current study was designed to evaluate the ability of three selective phosphodiesterase ( PDE ) type 4 inhibitors , rolipram , cilomilast and CI 1044 , to inhibit extracellular matrix degradation . using zymography and elisa , we found that pro MMP 2 release was enhanced following 24 h treatment of human lung fibroblast ( MRC 5 ) with TGF beta1 ( 10 ng / ml ) or TNF alpha ( 10 ng / ml ) , whereas PMA ( 0 . 02 microm ) had no effect . One hour of pre incubation with PDE4 inhibitors ( 10 microm ) induced an inhibition of TNF alpha stimulated pro MMP 2 release . zymography and immunoblotting revealed that fibroblasts cultured with PMA or TNF alpha released increased amounts of pro MMP 1 , whereas TGF beta1 had no effect . incubation with CI 1044 or cilomilast significantly prevented the TNF alpha increase in pro MMP 1 . these results suggest that PDE4 inhibitors are effective in inhibiting the pro MMP 2 and pro MMP 1 secretion induced by TNF alpha and might underline a potential therapeutic benefit of selective PDE4 inhibitors in …

Matrix metalloproteinase 9 expression in post hypoxic human brain capillary endothelial cells : H2O2 as a trigger and NF kappab … (2003 Sep)
matrix metalloproteinase 9 expression in post hypoxic human brain capillary endothelial cells : H2O2 as a trigger and NF kappab as a signal transducer . The haemorrhagic transformation in ischemic stroke involves disruption of the integrity of the microvascular beds , partially based on the action of matrix metalloproteinases ( MMPs ) . The objective of the present study was to evaluate the contribution of microvascular endothelial cells from human brain ( hbecs ) to MMPs expression and regulation under conditions relevant to brain ischemia . MMPs and their inhibitors were examined with zymography , western blotting , elisa and MMP activity assay in cultured hbecs . Four hour hypoxia ( pO ( 2 ) 60 mmHg ) elevated the level of MMP 9 in the supernatant of the hbecs and this early response required collagen matrix . active oxygen species sustained the increased MMP 9 activity for at least 24 h . In the post hypoxic period 20 micro mol / L H ( 2 ) O ( 2 ) caused a 6 fold increase in the specific activity of MMP 9 over the normoxic cells and a comparable effect was exerted by thrombin ( 50 nmol / L ) and leukocyte elastase ( 10 nmol / L ) . The role of NF kappab , a redox state sensitive transcription factor , was evaluated with immunofluorescence confocal microscopy and immunoblotting of nuclear and cytoplasmic extracts . The oxidative stress dependent MMP 9 induction was accompanied by a significant …

Matrix metalloproteinase 9 modulates intestinal injury in rats with transmural colitis. (2006 Apr)
matrix metalloproteinase 9 modulates intestinal injury in rats with transmural colitis . proteolysis and degradation of extracellular matrix by metalloproteinases ( MMPs ) may contribute to intestinal injury in inflammatory bowel disease . In the present study , we investigated the pathogenic role of gelatinases ( MMP 9 and MMP 2 ) on transmural colonic injury in a rat model of chronic colitis , which was induced by intracolonic instillation of trinitrobenzene sulfonic acid ( TNBS ) . The activity and expression of MMP 2 and MMP 9 were measured in colonic tissue and peripheral neutrophils by fluorescence , zymography , western blot , or immunohistochemistry at different time points . furthermore , myeloperoxidase content in colonic homogenates was analyzed to evaluate inflammation . finally , morphological changes were assessed following early or delayed administration of CGS 27023 A , a synthetic inhibitor of MMPs . We found that the induction of colitis led to a significant up regulation in tissue gelatinase concentration , whereas no changes in collagenase activity were observed . In addition , up regulation of pro MMP 9 , but not of pro MMP 2 , was found on Days 7 and 10 following the induction of colitis . furthermore , transmural MMP 9 was detected by immunofluorescent staining in the inflamed tissue . consistent with tissue samples , neutrophils from colitic rats showed a significantly increased activity of pro MMP 9 . finally , early but not delayed treatment with CGS 27023 A attenuated colonic …

Expression of matrix metalloproteinase 2 and 9 in liver tissue of patients with schistosomiasis japonica objective : To explore the … (2003 Nov)
expression of matrix metalloproteinase 2 and 9 in liver tissue of patients with schistosomiasis japonica objective : To explore the change of matrix metalloproteinase 2 ( MMP 2 ) and matrix metalloproteinase 9 ( MMP 9 ) expression in liver tissue of the patients with schistosomiasis japonica . methods : liver biopsy materials were examined pathomorphologically in 26 patients with schistosomiasis in advanced stage and 5 cases without the disease as control . The expression of MMP 2 , MMP 9 and C IV were studied by immunohistochemistry , and result was analyzed by picture quantitative analysis technique . results : immnoreactive MMP 2 was mainly expressed in the plasma , the membrane of hepatocytes and hepatic sinusoids , it was also found in myofibroblast cells and endothelial cells of blood vessel . immnoreactive MMP 9 was observed in hepatic stellate cells , sinusoids and myofibroblast cells , sometimes it was also seen in the plasma of hepatocytes and epithelial cells of bile duct . The expression of MMP 2 , MMP 9 and C IV was significantly stronger in patients with advanced schistosomiasis than that of the control ( P 0 . 05 ) . The expression of MMP 2 was relevant to the inflammation grade and stage of liver fibrosis ( P 0 . 01 ) . The expression of MMP 9 did not show significant change ( P 0 . 05 ) and the expression of C IV was consistent with that of MMP 2 . conclusion …

TNF alpha stimulates activation of pro MMP2 in human skin through NF ( kappa ) B mediated induction of MT1 … (2001 Jan)
TNF alpha stimulates activation of pro MMP2 in human skin through NF ( kappa ) B mediated induction of MT1 MMP . tumor necrosis factor alpha ( TNF ( alpha ) ) is an important mediator during the inflammatory phase of wound healing . excessive amounts of pro inflammatory cytokines such as TNF ( alpha ) are associated with inflammatory diseases including chronic wounds . matrix metalloproteinases ( MMPs ) are involved in matrix re modeling during wound healing , angiogenesis and tumor metastasis . As with pro inflammatory cytokines , high levels of MMPs have been found in inflammatory states such as chronic wounds . In this report we relate these two phenomena . TNF ( alpha ) stimulates secretion of active MMP 2 , a type IV collagenase , in organ cultured full thickness human skin . This suggests a mechanism whereby excess inflammation affects normal wound healing . To investigate this observation at the cellular and molecular levels , we examined TNF ( alpha ) mediated activation of pro MMP 2 , induction of MT1 MMP , and the intracellular signaling pathways that regulate the proteinase in isolated human dermal fibroblasts . We found that TNF ( alpha ) substantially promoted activation of pro MMP 2 in dermal fibroblasts embedded in type I collagen . In marked contrast , collagen or TNF ( alpha ) individually had little influence on the fibroblast mediated pro MMP 2 activation . One well characterized mechanism for pro MMP 2 activation …

Increased expression of matrix metalloproteinase 9 in neutrophils in glycogen induced peritoneal inflammation of guinea pigs. (2000 May)
increased expression of matrix metalloproteinase 9 in neutrophils in glycogen induced peritoneal inflammation of guinea pigs . objective : matrix metalloproteinase ( MMP ) 9 plays an important role in neutrophil extravasation and migration by its ability to degrade the major components of basement membrane . To evaluate the expression of neutrophil MMP 9 under inflammatory conditions , we examined the levels of MMP 9 and its mRNA in neutrophils of glycogen induced peritoneal inflammation . materials AND methods : Male hartley guinea pigs weighing 250 300 g were intraperitoneally injected with 0 . 17 glycogen solution , and 13 15 h after the injection , blood and peritoneal neutrophils were isolated . The levels of MMP 9 and its mRNA were analyzed by gelatin zymography and northern blotting , respectively . furthermore , MMP 9 activities in the peritoneal supernatants were measured . results : MMP 9 level in peritoneal neutrophils was essentially the same as that in blood neutrophils , although peritoneal neutrophils were assumed to have extracellularly released MMP 9 from the granules during infiltration into the peritoneal cavity . interestingly , MMP 9 mRNA was expressed more abundantly in peritoneal neutrophils than in blood neutrophils ( p 0 . 01 ) . moreover , MMP 9 levels in blood and peritoneal neutrophils were reduced to 30 45 of non treated controls by actinomycin D ( 500 microg / kg ) or cycloheximide ( 10 mg / kg ) treatment ( p 0 . 05 ) . …

Activated gelatinase B ( MMP 9 ) and urokinase type plasminogen activator in synovial fluids of patients with arthritis. (1995 Jul)
activated gelatinase B ( MMP 9 ) and urokinase type plasminogen activator in synovial fluids of patients with arthritis . correlation with clinical and experimental variables of inflammation . objective : To evaluate the occurrence of gelatinase B ( matrix metalloproteinase 9 , MMP 9 ) in synovial fluids ( SF ) of patients with arthritis to investigate the possible role of this neutral MMP in joint destruction . methods : In paired ( series I ) and unpaired SF ( series II ) we examined the occurrence of gelatinase B , prostromelysin 1 , and urokinase type plasminogen activator ( u PA ) . results : In the paired SF a parallelism between the presence of activated gelatinase B and the local arthritis activity scores of the knees was observed . activated gelatinase B correlated well with the presence of stromelysin 1 and u PA , 2 enzymes probably involved in the activation process of gelatinase B . In the 2nd series , activated gelatinase B was found in 56 SF samples , whereas 82 samples did not exhibit activated gelatinase B . The SF samples with the activated form of gelatinase B showed a significantly higher ability to induce permeability changes in cultured monolayers of human endothelial cells , had more myeloperoxidase activity secreted by infiltrated leukocytes and had higher u PA antigen concentrations , compared to SF samples without the activated form of gelatinase B . conclusion : Our data suggest that the presence of gelatinase B …

Contribution of alveolar macrophages to the response of the TIMP 3 null lung during a septic insult. (2007 Aug)
contribution of alveolar macrophages to the response of the TIMP 3 null lung during a septic insult . Mice deficient in tissue inhibitor of metalloproteinase 3 ( TIMP 3 ) develop an emphysema like phenotype involving increased pulmonary compliance , tissue degradation , and matrix metalloproteinase ( MMP ) activity . after a septic insult , they develop a further increase in compliance that is thought to be a result of heightened metalloproteinase activity produced by the alveolar macrophage , potentially modeling an emphysemic exacerbation . therefore , we hypothesized that TIMP 3 null mice lacking alveolar macrophages would not be susceptible to the altered lung function associated with a septic insult . TIMP 3 null and wild type ( WT ) mice were depleted of alveolar macrophages before the induction of a septic insult and assessed for alteration in lung mechanics , alveolar structure , metalloproteinase levels , and inflammation . The results showed that TIMP 3 null mice lacking alveolar macrophages were protected from sepsis induced alterations in lung mechanics , particularly pulmonary compliance , a finding that was supported by changes in alveolar structure . additionally , changes in lung mechanics involved primarily peripheral tissue vs . central airways as determined using the flexivent system . From investigation into possible molecules that could cause these alterations , it was found that although several proteases and inflammatory mediators were increased during the septic response , only MMP 7 was attenuated after macrophage depletion . In conclusion , the …

Insulin like growth factor binding protein 5 is a target of matrix metalloproteinase 7 : implications for epithelial mesenchymal signaling. (2005 Aug)
insulin like growth factor binding protein 5 is a target of matrix metalloproteinase 7 : implications for epithelial mesenchymal signaling . matrix metalloproteinase 7 ( MMP 7 ) is localized to epithelial cells and is up regulated in many cancers and in inflammation . We now report that MMP 7 targets a key mesenchymal cell type , the myofibroblast . recombinant MMP 7 stimulated the proliferation and migration of human colonic myofibroblasts . these responses were partly attributable to activation of other MMPs , notably MMP 3 and MMP 8 , and to stimulation of the mitogen activated protein kinase and phosphatidylinositol 3 kinase signaling pathways . using a proteomic approach , we identified insulin like growth factor binding protein 5 ( igfbp 5 ) as a previously unsuspected target of MMP 7 produced by colonic myofibroblasts . We present evidence that the MMP 7 cleavage of igfbp 5 liberates IGF II that functions as an autocrine myofibroblast growth factor . Thus , MMP 7 may act as a signal from epithelial cells for local recruitment of myofibroblasts and stimulation of their proliferation . similar effects of MMP 7 produced in epithelial tumors might account for the expansion of stroma through activation of myofibroblasts .

Matrix metalloproteinases , tissue inhibitors of matrix metalloproteinases and angiogenic cytokines in peripheral blood of patients with thyroid cancer. (2002 Sep)
matrix metalloproteinases , tissue inhibitors of matrix metalloproteinases and angiogenic cytokines in peripheral blood of patients with thyroid cancer . stimulation of growth of endothelial cells from preexisting blood vessels , i . e . , angiogenesis , is one of the essential elements necessary to create a permissive environment in which a tumor can grow . during angiogenesis , the matrix metalloproteinase ( MMP ) family of tissue enzymes contributes to normal ( embriogenesis or wound repair ) and pathologic tissue remodeling ( chronic inflammation and tumor genesis ) . The proposed pathogenic roles of MMPs in cancer are tissue breakdown and remodeling during invasive tumor growth and tumor angiogenesis . tissue inhibitors of metalloproteinases ( timps ) form a complex with MMPs , which in turn inhibits active MMPs . vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) are unique among mediators of angiogenesis with synergistic effect , and both can also be secreted by thyroid cancer cells . The goal of the study was to evaluate the plasma blood concentration of VEGF , bFGF , MMP 1 , MMP 2 , MMP 3 , MMP 8 , MMP 9 , TIMP 1 , and TIMP 2 in patients with cancer and in normal subjects . twenty two patients with thyroid cancers ( papillary cancer , 11 ; partly papillary and partly follicular cancer , 3 ; anaplastic cancer , 5 ; medullary cancer , 3 ) and 16 healthy subjects …

Matrix metalloproteinases collagenase 2 , macrophage elastase , collagenase 3 , and membrane type 1 matrix metalloproteinase impair clotting by … (2000 Nov)
matrix metalloproteinases collagenase 2 , macrophage elastase , collagenase 3 , and membrane type 1 matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII . The effects of plasma proteins on controlling the activity of matrix metalloproteinases ( MMPs , matrixins ) have been the focus of numerous studies , although only a few have examined the influence of matrixins on plasma proteins . recently , it has been shown that MMPs may play a role in the degradation of fibrin . We have now investigated the role of collagenase 2 ( MMP 8 ) , macrophage elastase ( MMP 12 ) , collagenase 3 ( MMP 13 ) , and membrane type 1 matrix metalloproteinase ( MT1 MMP , MMP 14 ) in the degradation of fibrinogen and factor XII of the plasma clotting system . Our data demonstrate that the catalytic domains of MMP 8 , MMP 12 , MMP 13 , and MMP 14 can proteolytically process fibrinogen and , with the exception of MMP 8 , also inactivate factor XII ( hageman factor ) . We have identified the amino termini of the major protein fragments . cleavage of fibrinogen occurred in all chains and resulted in significantly impaired clotting . moreover , rapid proteolytic inactivation of factor XII ( hageman factor ) by MMP 12 , MMP 13 , and MMP 14 was noted . these results support the hypothesis of an impaired thrombolytic potential of MMP degraded factor XII in vivo . …