Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a human melanoma metastasis model in nude mice. In this model, a human variant cell line (451-LU) was obtained that spontaneously metastasized in nude mice. This variant cell line was selected from the lung of a nude mouse after several in vivo passages of human melanoma WM164 cells previously isolated from a melanoma metastasis of a patient. The WM164 cells were not competent for metastasis in nude mice prior to this selection. We compared the phenotypes of the parental nonmetastatic cell line and the metastatic variant with respect to growth at clonal seeding densities in protein-free medium (growth factor independence), in vitro invasion through reconstructed basement membranes, secretion of proteolytic enzymes, expression of tumor-associated antigens, and chromosomal abnormalities. Metastatic 451-LU cells showed significantly increased growth factor independence when grown at clonal seeding densities as compared to the parental cells. In in vitro chemoinvasion assays, metastatic 451-LU cells were significantly more invasive than the parental cells. The metastatic variant secreted collagenase and tissue type plasminogen activator at levels 10- and 3-fold higher than the parental WM164 cells, respectively. Polyclonal antibodies to tissue type plasminogen activator significantly inhibited invasion through reconstructed basement membranes. In metastatic 451-LU cells, expression of nerve growth factor receptor was elevated, both at the protein and transcriptional level. Metastatic cells were aneuploid with a mode of 97 chromosomes, whereas the parental nonmetastatic cells had a mode of 52 chromosomes. Our studies suggest that metastatic melanoma cell variants selected in vivo show increased independence of exogenous growth factors when grown at clonal cell densities, enhanced invasiveness in vitro, greater secretion of proteolytic enzymes, and increased chromosome mode as compared to the nonmetastatic parental cells. The data further suggest that melanoma cells isolated from metastatic lesions and maintained in vitro have an unstable invasive phenotype but that metastatic variant cells can readily be selected.
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PMID:In vitro properties of human melanoma cells metastatic in nude mice. 215 14

Previous studies showed that acute administration of O,O,S trimethyl phosphorothioate (OOS-TMP), a contaminant in malathion, acephate and fenitrothion, led to increases in metabolic activities, such as, secretion of interleukin 1 and nonspecific esterase, of splenic and peritoneal macrophages. In this report, the effect of OOS-TMP administration on the levels of the neutral proteases, elastase, collagenase and plasminogen activator, in cultures supernatants of peritoneal and splenic macrophages is presented. Acute administration of OOS-TMP elevated collagenase levels only at day 3 following treatment with 10 or 20 mg/kg OOS-TMP. Levels of elastase in culture supernatant of peritoneal and splenic macrophages, on the other hand, was elevated at days 1, 3, 5 and 7 following administration of OOS-TMP. The effect on elastase secretion was dose-dependent at days 5 and 7 after treatment. Levels of plasminogen activator activity in the culture supernatants of splenic macrophages was elevated at day 5 following treatment with both doses of OOS-TMP. At days 1 and 3, the level of plasminogen activator inhibitor was suppressed. However, at days 5 and 7 plasminogen activator inhibitory activity was close to control values. These data show that OOS-TMP administration led to an elevation in the levels of neutral proteases in culture supernatants of peritoneal and splenic macrophages. This elevation indicates that acute OOS-TMP administration alters another parameter of macrophage function, which is elevated following exposure to acute inflammatory stimuli.
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PMID:Modulation of macrophage protease activity by acute administration of O,O,S trimethyl phosphorothioate. 216 Jan 88

Levels of tissue inhibitor of metalloproteases (TIMP) and plasminogen activator (PA)/plasmin were measured and the distribution of PA was studied by immunohistochemical techniques in cartilage and synovium samples from dogs subjected to sectioning of the anterior cruciate ligament of their right knees and sham operation of their left knees (controls). Twenty-three animals were divided into 3 groups and killed at 2, 4, or 8 weeks after surgery. The levels of PA and plasmin were found to be significantly elevated in the osteoarthritic (OA) knee cartilage and synovium at all times after surgery, except for levels of PA in the OA cartilage at 2 weeks. There was a positive correlation between the levels of PA and plasmin in the synovial membrane (r = 0.64, P less than 0.001). In OA knees, the presence of high levels of total and active collagenase was detected in cartilage and in synovium. The levels of these 2 forms of collagenase showed a positive correlation both in cartilage (r = 0.65, P less than 0.001) and in synovium (r = 0.77, P less than 0.001). The levels of TIMP in cartilage from OA and sham operated knees were similar. Although the TIMP level was increased in the OA synovium, it was found only in trace amounts in cartilage. Immunohistochemical studies revealed that both forms of PA, urokinase-type PA and tissue-type PA, and TIMP were present in OA tissues. In the synovium, they were found mainly in monocyte/macrophages, synovial lining cells, and blood vessel cells. In OA cartilage, PA was present only at the superficial level in chondrocytes and in cartilage matrix, whereas TIMP was present in chondrocyte lacunae throughout the full thickness of the cartilage. TIMP was also detected in the superficial level of cartilage from sham operated knees. The results of this study indicate that in OA tissues, there are conditions that favor the synthesis and activation of metalloproteases. PA and plasmin are likely to play an important role in the physiologic activation of metalloproteases, although they are probably not the only system involved in this process. The lack of increased TIMP levels in the OA cartilage, in the presence of increased metalloprotease activity, is also a possible contributing factor in the enzymatic degradation of this tissue.
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PMID:Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis. 217 38

Collagenase has been implicated in colonic anastomotic dehiscence but the enzyme has not previously been specifically measured in colonic healing. A 72 h tissue culture method for colonic tissue and a radiochemical assay for collagenase were adapted to measure the enzyme in healing rabbit colon, with specificity of the assay confirmed by sodium dodecylsulphate polyacrylamide gel electrophoresis. Normal and postoperative colon secreted collagenase, predominantly in a latent form, in the first 24 h of culture. Total activity reached a plateau after 48 and 72 h in culture, when 50-70 per cent of the enzyme was in an active form. At these times in culture, activity was significantly higher than after 24 h (P less than 0.001). One day after anastomosis the total amount of collagenase secreted in culture was higher than normal but the increase did not achieve significance. Three days after anastomosis the colon secreted more collagenase than explants from 1 day postoperative tissue (P less than 0.002). The proportion of active enzyme in the first 24 h in culture was also increased. Since active collagenase can be measured in culture medium from both normal and postoperative colon, the tissue may be secreting plasminogen activator which allows plasmin to activate the enzyme. The increase in collagenase after operation coincided with a decrease in collagen concentration in the colon wall, measured by hydroxyproline. This supports previous suggestions that collagenase contributes to anastomotic dehiscence. However, the findings must be interpreted with caution as the variance of the results was shown to be predominantly due to time in culture, suggesting this could be a bigger influence than the operation itself. In addition, our previously reported immunohistochemical study of this system indicated that collagenase only occurred in a localized region, restricted to the everted portion of the anastomosis, with the activity being tightly controlled by its inhibitor, tissue inhibitor of metalloproteinases.
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PMID:Direct measurement of collagenase in colonic anastomosis. 217 9

Recent studies have indicated that neutral collagenase can be produced in bones of rats. In addition, it has been demonstrated by in vitro studies that the enzyme is likely secreted by osteoblasts. Cells of the osteoblastic tumor cell line UMR-106 can be stimulated to produce not only collagenase, but also collagenase inhibitor and plasminogen activator. However, it is conceivable that not all osteoblasts produce all of these proteins. In this study, in which UMR cells were maximally stimulated with PTH, only a subpopulation of cells was observed to produce enhanced levels of collagenase but all cells had the ability to synthesize plasminogen activator. Cells of the rat osteosarcoma line UMR-106-01 were stained for the presence of collagenase and tissue plasminogen activator using an immunohistochemical procedure. In many cases, the cells were exposed to monensin for the final 3 h of incubation as well as to the inducing agent PTH. Monensin prevented export of the enzymes, enabling them to be visualized within their cell or origin. Maximal stimulation of collagenase was demonstrated to occur 8 h after exposure to 10(-8) -10(-7) M PTH. Under these conditions, 14-17% of the cells appeared to synthesize elevated amounts of collagenase (as determined by intense staining). Without PTH stimulation, there was a low level of collagenase in all cells, but less than 1% of the cells stained heavily for the enzyme. In contrast, strong staining for plasminogen activator was observed in all cells with or without PTH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of collagenase production by rat osteosarcoma cells can occur in a subpopulation of cells. 217 54

A crucial event during angiogenesis is the invasion of the perivascular extracellular matrix by sprouting endothelial cells. To investigate the possible role of proteases in endothelial cell invasiveness in vitro, bovine microvascular endothelial cells (BMEC) grown on collagen gels were treated with phorbol myristate acetate (PMA), a tumor promoter that markedly increases their production of collagenase and plasminogen activator. Whereas control BMEC were confined to the surface of the gels, PMA-treated BMEC invaded the underlying collagen matrix, where they formed an extensive network of capillary-like tubular structures. This phenomenon, which mimics some of the events occurring during angiogenesis in vivo, required protein synthesis and intercellular contact, was accompanied by collagen degradation, and was prevented by the metalloprotease inhibitor 1,10-phenanthroline.
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PMID:Tumor-promoting phorbol esters induce angiogenesis in vitro. 241 23

A crude extract of human placenta has been demonstrated to stimulate growth, motility and the production of the proteases plasminogen activator and collagenase in cultured bovine capillary endothelial cells. These data are in keeping with the presence of an angiogenic factor(s) in human placenta.
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PMID:Human placental tissue stimulates bovine capillary endothelial cell growth, migration and protease production. 241 39

Using a novel method, a monoclonal antibody was produced which can directly block the activity of an extracellular matrix-associated neurite outgrowth promoting complex (Matthew and Patterson, 1983). Presumably binding at or near the active site, this antibody recognizes a determinant consisting of heparan sulfate and a larger molecule which is likely to be laminin (Matthew et al., in preparation). The antibody has been further used to localize this determinant in adult tissues in vivo. Extracellular binding is seen at sites known to promote axon regeneration in the peripheral nervous system and is not seen in the central nervous system (Matthew et al., in preparation). In investigating how neurons may modify their environment as they grow processes, we have recently found that sensory and sympathetic neurons spontaneously release a collagenase and a plasminogen activator from their distal processes and/or growth cones (Pittman, 1985). A 43 kD irreversible inhibitor of the plasminogen activator is secreted by cardiac myocytes and is found on the surfaces of cultured neurons (Pittman, 1984). This inhibitor is also released by nonneuronal cell cultures from peripheral, but not central, nerves (Pittman, unpublished). Of interest in relation to the proteoglycan neurite outgrowth promoting complex is the finding that the 43 kD inhibitor preparation binds heparin tightly and can displace laminin from its heparin binding site (Patterson and Pittman, unpublished). Thus it is possible that the protease/inhibitor system could affect outgrowth via interaction with the neurite outgrowth promoting complex in the extracellular matrix.
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PMID:On the role of proteases, their inhibitors and the extracellular matrix in promoting neurite outgrowth. 242 54

We present a cascade of proteolytic events catalyzed by the proteases secreted by cultured keratinocytes and fibroblasts that results in the activation of interstitial procollagenase. Cultured human skin fibroblasts constitutively secrete interstitial collagenase and stromelysin as proenzymes. In contrast, interstitial collagenase found in serum-free skin organ culture conditioned medium is activated. Cocultivation of the major cellular components of skin organ culture, dermal fibroblasts and epidermal keratinocytes, induces activation of interstitial procollagenase and prostromelysin in the presence of plasminogen. This activation occurs through a urokinase-dependent pathway where added keratinocytes secrete the plasminogen activator urokinase, which converts plasminogen into plasmin. Plasmin is capable of activating purified procollagenase and prostromelysin. Plasmin-dependent activation of procollagenase generates an enzyme species, by amino-terminal processing, identical to those generated by limited proteolysis with trypsin or treatment with organomercurial compounds. Catalytic amounts of activated stromelysin can in turn convert plasmin- or trypsin-activated collagenase into a fully active enzyme by removal of approximately 15 amino acid residues from the carboxyl end of the enzyme. This results in a 5- to 8-fold increase in collagenase specific activity that is due to its proteolytic cleavage and not to the presence of the activator stromelysin. Stromelysin alone in both pro- and activated forms is not capable of efficient activation of human fibroblast interstitial procollagenase.
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PMID:Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. 246 56

Human lung cancer cell line, named KUM.LK-2 was established from xenograft implanted in nude mice and maintained for 43 months. And serially transplanted in nude mice. This line has the following biological characters. 1) Spontaneous lung metastases are made in nude mice inoculated subcutaneously. 2) This line can produce some kinds of proteases, like as tissue type plasminogen activator, urokinase type plasminogen activator and collagenase. 3) KUM.LK-2 has the ability of platelet aggregation.
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PMID:[Establishment and characterization of human lung cancer cell line (KUM.LK-2)]. 248 63


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