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)

The tissue-destructive proteinases of B16-BL6 melanoma cells from C57BL/6 mice and subcellular fractions were examined. Cancer cell organelles were isolated following nitrogen cavitation with the use of sucrose density gradient centrifugation. Serine, cysteine, and metalloproteinases were assayed with the use of radiolabeled proteins and synthetic substrates. Tumor-induced red blood cell lysis was quantitated by measurement of the release of isotope from 59Fe-labeled red blood cells (RBC) cocultivated with melanoma cells; the RBC were from Wistar rats. Enzyme inhibitors with specificity toward different classes of proteinases were used in the above assays to categorize the enzymes responsible for substrate degradation. Results indicated that intact melanoma cells, cell organelles, and cytosol contain proteinases that can degrade collagen and gelatin and lyse normal RBC. Melanoma plasma membranes are highly enriched in collagenase, gelatinase, cysteine proteinase, plasminogen activator, and cytolytic activity. The inhibition of tumor collagenolytic, gelatinolytic, and cytolytic activities by EDTA and 1,10-phenanthroline but not by diisopropyl fluorophosphate and N alpha-p-tosyl-L-lysine chloromethyl ketone indicates that metalloproteinases are the active enzymes in these assays. Minocycline, a synthetic tetracycline with demonstrable inhibitory activity with other mammalian collagenases, also inhibited melanoma collagenolytic and cytolytic activities.
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PMID:Diversity of melanoma plasma membrane proteinases: inhibition of collagenolytic and cytolytic activities by minocycline. 299 28

Prediction of early metastases in individual patients has been attempted by combined evaluation of a battery of recognised parameters such as blood vessel invasion (BVI) of tumor cells, Barr body frequency (BBF), plasminogen activator (PA), collagenase, estradiol receptors (ER), progesterone receptors (PgR), and peroxidase activity (PRA) in 18 malignant and 3 benign (control) breast tumors. Since breast tumor cells spread through the blood vessels, the cases were divided into BVI (+) and BVI (-) groups. Results show that in the former group, all the cases had poor prognosis and two even had distant metastases within one year. In BVI (-) group, 9 out of 12 appeared to have good prognosis.
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PMID:Prediction of biological behaviour of human breast cancer using multiple parameters. A preliminary study. 299 51

The interstitial collagens are degraded predominantly extracellularly, by specific collagenases (metalloproteinases) capable of cleaving the helical region across the three chains at a similar locus, solubilizing the cleaved products from the fibril. Other neutral proteinases may also function in this role by cleaving near cross-links in the fibril. Collagen type, molecular aggregation and small changes in temperature all markedly affect rates of collagenolysis in the fibril. Regulation of collagenolysis is also modulated at the levels of (1) cellular production of latent collagenase (procollagenase), (2) activation of latent collagenase, and (3) production of collagenase inhibitors. Fibroblastic cells and certain macrophages are probably the predominant sources of collagenases in inflammation; an enzyme in polymorphonuclear leucocytes (neutrophils) is distinct from the tissue enzyme. Molecules such as mononuclear cell factor (MCF), homologous with interleukin 1, which augment cellular collagenase production in inflammation, are derived from monocytes. The mechanisms of augmented collagenase production involve new protein synthesis and, if this augmentation is analogous to that produced by urate crystals, it is probably associated with increased levels of procollagenase mRNA. MCF production is itself controlled by products of lymphocytes as well as by interactions of monocytes with the Fc portion of immunoglobulins and components of the extracellular matrix. Activation of latent (pro)collagenase probably occurs in vivo through the action of neutral proteinases such as plasmin (through plasminogen activator). These effects may be indirect and exerted through proteolytic activation of a procollagenase activator. Tissue inhibitors act to regulate the active collagenase.
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PMID:The turnover and degradation of collagen. 299 13

The chick chorioallantoic membrane (CAM) was used as an assay system to examine the invasive potential of human choriocarcinoma cell lines. When 5 X 10(6) cells were inoculated into the CAM at the 10th day of postfertilization, three of eight cell lines formed extensively invasive tumors within the CAM. A tendency to correlation between the tumorigenic potential of cell lines in hamster cheek pouches and their invasive potential in the CAM was noted. In addition, the invasive capacity of cell lines correlated well with the amount of collagenase but did not correlate with the amount of plasminogen activator or cathepsin B secreted by them. It is concluded that a heterogeneity of invasive potential in the CAM exists among human choriocarcinoma cell lines and the role of the collagenase secreted by them is suggested.
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PMID:Invasion potential of human choriocarcinoma cell lines and the role of lytic enzymes. 299 58

The intense stromal response to some human tumors is termed the desmoplastic reaction. It is found with most human breast carcinomas. Dissolution of this response, containing predominantly fibrous proteins such as collagen and elastin, can occur with treatment. We have undertaken a study of the collagenases of the breast tumor desmoplastic reaction using a tissue culture model composed of human breast tumor cell lines and various human fibroblasts. The breast tumor cells had the higher collagenase activity, particularly the ZR75-31A cell line. Activity was 10-fold higher than that of the stromal cells. The enzyme was secreted into the media and required trypsin pretreatment for activity to be manifest. Partial purification was achieved of the major collagenase species. The protein was a metalloprotease and, like other mammalian collagenases, had a relative molecular weight of 60,000. Classical 3/4 and 1/4 cleavage products of the triple helical collagen substrate were demonstrated, typical of most mammalian collagenases. Only types I and III collagens were suitable substrates for this enzyme, with no apparent preference between the two. The breast tumor collagenases were not responsive to hormones; however, stimulation of activity was apparent in the absence of proteolytic pretreatment. This may represent conversion of the procollagenases of the breast tumor cells to the active form by an estrogen-sensitive plasminogen activator secreted by the same tumor cells.
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PMID:Collagenases in human breast carcinoma cell lines. 300 15

The purpose of this study was to adduce further evidence for a paracrine role for human decidual relaxin (Rlx) in the remodelling of collagen in the fetal membranes in the peripartal period. The binding of [125I]porcine Rlx to membrane-enriched fractions from fetal membranes as well as from dispersed cells from the fetal membranes was used to demonstrate the presence of specific Rlx receptors. Rlx added in vitro to cultured amnion/chorion cells increased the release of plasminogen activator and collagenase into the medium. Rlx had no effect on the release of beta-glucuronidase. An in vivo correlate of these in vitro results was obtained, the detection of plasminogen activator and collagenase in amniotic fluids. The active fraction of collagenase was increased in amniotic fluids collected after spontaneous rupture of the membranes. PRL, hCG, estrogen, and progesterone added in equimolar amounts to cultured amnion/chorion cells from elective cesarean sections and normal term deliveries also effected the release of plasminogen activator and collagenase. The greatest effects were found in cells from cesarean section tissue, in terms of the stimulation of plasminogen activator release by Rlx and PRL and of collagenase release by prostaglandin F2 alpha and, to a lesser extent, by Rlx, PRL, and hCG. We conclude that human fetal membranes are targets for a number of hormones, including the decidual paracrine hormones Rlx, PRL, and prostaglandin F2 alpha as well as estrogen, progesterone, and hCG. These hormones act to release or inhibit the enzymes involved in collagen breakdown before rupture of the fetal membranes.
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PMID:The human fetal membranes: a target tissue for relaxin. 300 43

Early-passage human foreskin fibroblasts were exposed to X-ray doses ranging from 100 to 600 rad. The X-ray treatments resulted in cell killing in a dose-dependent manner as judged by the colony-forming efficiency of the cells. When cultures exposed to radiation were serially passaged and checked at various times for growth in semi-solid medium they showed the presence of cells with the ability to grow under anchorage-independent conditions (in agarose) at 24 population doublings. The frequencies of colonies with the ability to grow in agarose increased with increasing doses of X-rays above the levels observed for control cultures under similar conditions. When assayed for plasminogen activator levels, the X-ray-treated cultures at various passages showed insignificant differences from levels observed in control cultures. However, the amounts of collagenase (type IV collagen-specific) increased significantly by 32 population doublings in the X-ray-treated cultures compared with control cultures. Our results suggest that the production of type IV collagen-specific collagenase could be useful as an in vitro marker for the transformation of human diploid fibroblasts by X-irradiation.
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PMID:Radiation-induced anchorage-independent growth and collagenase production in diploid human fibroblasts. 300 74

In the current study we have measured collagenase activity released from skin explants and fibroblasts of patients with both Guam-type and sporadic amyotrophic lateral sclerosis and controls. The rationale for such a study derives from work reported more than 20 years ago demonstrating abnormalities in skin collagen metabolism in patients with the disease. We were not able to find significant differences in collagenase activity when fibroblasts were compared relative to the total protein secreted. This is explained, in part, by our finding of an increase in total protein released from fibroblasts of the amyotrophic lateral sclerosis patient group. Increased collagenase release did occur when activity was expressed per number of cells plated but was not statistically significant. In addition, increased release followed a 3-day lag period in skin organ culture. These results suggest that collagenase and other enzymes known to activate collagenase, such as plasminogen activator, capable of degrading extracellular matrix components might be responsible for the increased collagenolytic activity previously observed in amyotrophic lateral sclerosis patients' skin. Further evaluation of extracellular-acting degradative enzymes from skin, muscle, nerve and central nervous system may be important to follow-up such leads in understanding the pathogenesis of this enigmatic and fatal disorder.
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PMID:Collagenase activity in skin fibroblasts of patients with amyotrophic lateral sclerosis. 300 15

A protein that stimulates the production of plasminogen activator and latent collagenase in cultured bovine capillary endothelial cells has been purified 10(6)-fold from term human placenta by using a combination of heparin affinity chromatography, ion-exchange chromatography, and gel chromatography. The purified molecule has a molecular weight of 18,700 as determined by NaDodSO4/PAGE under both reducing and nonreducing conditions. The purified molecule stimulates the production of plasminogen activator and latent collagenase in a dose-dependent manner between 0.1 and 10 ng of protein/ml. The purified protein also stimulates DNA synthesis and chemotaxis in capillary endothelial cells in the same concentration range. Thus, this molecule has all of the properties predicted for an angiogenic factor.
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PMID:Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis, and migration. 300 51

Several crude angiogenesis preparations, as well as a purified angiogenesis factor from human placenta, were tested for their ability to stimulate the production of plasminogen activator (PA) and collagenase activities, motility, chemotaxis, DNA synthesis and clonal growth in cultured endothelial cells. Treatment of capillary endothelial cells resulted in a stimulation of all the above activities, whereas endothelial cells derived from large vessels did not respond. These cellular activities are postulated to be responsible for capillary growth in vivo.
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PMID:Purification and biological activities of an angiogenesis factor from human placenta. 301 26


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