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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The secretory glycoproteins synthesized by hepatoma tissue culture (HTC) cells were resolved by two-dimensional polyacrylamide gel electrophoresis of media from cells that were grown in the presence of [(3)H]fucose. These cells synthesize and secrete a complex set of fucose-containing glycoproteins. These secretory glycoproteins are distinct from those glycoproteins present in the plasma membrane of HTC cells. Incubation of HTC cells with dexamethasone has a pronounced effect on the quality and quantity (denoted here as the program) of secretory protein synthesis, as assayed by the short-term incorporation of labeled mannose, fucose, or methionine. The synthesis of two mannose- and fucose- containing glycoprotein series, one of 50,000 mol wt and a more heterogeneous series with mol wt of 35,000-50,000, is increased to a high level by the hormone; conversely, the synthesis of other secretory proteins, particularly one with mol wt of 70,000, is decreased or stopped completely. The synthesis of some major secretory proteins is not affected by the hormone. Dexamethasone has less of an effect on the composition of either total cell membrane glycoprotein or plasma membrane glycoprotein. But there is a decrease in the synthesis of a major membrane glycoprotein series with mol wt of 140,000. These effects of dexamethasone are relatively specific to HTC cells. Neither Reuber H-35 cells nor primary cultures of rat hepatocytes show the same response to the steroid. Two variant HTC cell lines, which were selected for their resistance to dexamethasone inhibition of extracellular plasminogen activator activity, respond only partially to the steroid-induced regulation of the secretory and membrane glycoproteins.
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PMID:Dexamethasone regulates the program of secretory glycoprotein synthesis in hepatoma tissue culture cells. 624 97

Mammalian conceptuses must provide a chemical signal to the maternal system to insure maintenance of corpus luteum (CL) function and of progesterone production and continuation of uterine endometrial secretory activity. These events insure that the developing conceptus is provided with appropriate nutrients, regulatory enzymes and endocrine state to allow successful establishment and maintenance of pregnancy. Pig blastocysts begin to produce estrogens by Day 11 of pregnancy, which prevents secretion of the uterine luteolytic factor (PGF2 alpha) in an endocrine direction, but allows secretion in an exocrine direction, i.e., into the uterine lumen. Therefore, CL are "protected." Blastocyst estrogens also trigger secretion of a group of proteins, including uteroferrin, an iron transport protein, and a family of protease inhibitors whose biosynthesis within the uterine glandular epithelium is under the control of progesterone. Estrogen also appears to promote accumulation of glucose and fructose within the uterine lumen. A complex in vivo "culture medium" is thereby established to promote conceptus development. Pig blastocysts do not undergo invasive implantation within the uterine lumen although they produce the protease, plasminogen activator. Invasion may be prevented by endometrial secretion of progesterone-induced protease inhibitors which are produced in large amounts. In addition to estrogens of conceptus origin, calcium and prostaglandins PGF2 alpha and E2 may affect the uterine vasculature, water and electrolyte transport, capillary permeability, conceptus steroid production, and related events during pregnancy. The blastocysts of the large domestic animals also secrete proteins which include a large glycoprotein (Mr approximately 600,000) and a small acidic protein (Mr approximately 17,000). The latter has been purified from sheep and named ovine trophoblast protein I. These proteins may play unique roles in early pregnancy with respect to establishment and maintenance of pregnancy in the ewe, sow, mare, and cow.
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PMID:Biochemical aspects of conceptus--endometrial interactions. 636 10

Medium conditioned by bovine arterial endothelial cells inhibited the degradation by human fibrosarcoma cells of living cultures of rat smooth muscle cells or their cell-free extracellular matrices. Endothelial cell-conditioned medium had no effect on the growth kinetics of fibrosarcoma cells, and the inhibitory influence of conditioned medium on matrix degradation was greatest with low numbers of tumor cells. Conditioned medium inhibited the production of tumor cell plasminogen activators, enzymes previously found to play a role in matrix glycoprotein degradation. The endothelial factor was heat- and acid-stable and non-dialyzable, and mixing experiments showed that it did not directly inactivate the tumor cell plasminogen activator. Endothelial cells may therefore modulate the production of proteolytic enzymes important in the implantation stage of tumor metastasis.
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PMID:Inhibition by bovine endothelial cells of degradation by HT-1080 fibrosarcoma cells of extracellular matrix proteins. 641 40

Cultured bovine aortic endothelial cells are associated with an unusually stable fibrinolytic inhibitor (Loskutoff, D.J., van Mourik, J.A., Erickson, L.A., and Lawrence, D. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2956-2960). This inhibitor was purified to apparent homogeneity from medium conditioned by these cells by a combination of concanavalin A affinity chromatography and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is a single-chain glycoprotein of apparent Mr 50,000 +/- 2,500 and isoelectric point of 4.5-5.0, and inhibits the ability of both urokinase and tissue-type plasminogen activator to cleave and active plasminogen. This inhibition of plasminogen activator activity is associated with the formation of an enzyme-inhibitor complex which can be detected after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified inhibitor retains full activity after incubation in the presence of 0.1% sodium dodecyl sulfate, or at pH 2.7, two treatments which rapidly destroy the activity of protease nexin, another cellular inhibitor of fibrinolysis. The inhibitor purified from cloned endothelial cells cultured in the presence of L-[3,4,5-3H]leucine represented 2.5-12% of the total radiolabeled protein released by the cells in a 24-h period. These results indicate that cultured bovine aortic endothelial cells synthesize and secrete a protein which inhibits plasminogen activators and is distinct from protease nexin. It is a major endothelial cell product, and, as such, probably plays an important role in regulating the fibrinolytic system of these cells.
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PMID:Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. 643 6

In order to clarify the origin and release mechanism of plasminogen activator in the tracheobronchial secretion of rats, electrophoretic analysis of the secretion and studies on the effects of certain vasoactive drugs on the activator activity in the secretion were carried out. From the results of electrophoretic analysis of the tracheobronchial secretion in non-treated rats, protease inhibitor composed of glycoprotein was not contained in the secretion in contrast to the circulating blood, but a protein of low molecular weight like albumin in the circulating blood was contained in the secretion. Furthermore, after injection of noradrenalin, the blood pressure was temporarily elevated and the fibrinolytic activity of the euglobulin fraction in the circulatory blood was also increased. Subsequent to this elevation of fibrinolytic activity in the circulating blood, the fibrinolytic activity in the tracheobronchial secretion increased. Based on these results, it is suggested that the increase of fibrinolytic activity in the circulating blood was due to increased release of plasminogen activator from the vascular wall, and the increased fibrinolytic activity of the tracheobronchial secretion was caused by a consequent increased transudation of plasminogen activator from the circulating blood into the tracheobronchial lumen.
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PMID:Interaction of fibrinolytic activity between the tracheobronchial secretion and circulating blood of rats. 653 52

In the MCF7 human breast cancer cell line, estradiol stimulates the synthesis of a 52 K secretory glycoprotein and has been reported to increase the plasminogen activator (PA) activity in the culture medium. Since one PA isozyme has a molecular weight close to 52 000 daltons under denaturing conditions, we asked whether the 52 K protein was a PA. The PA activity released in serum-free conditioned medium was evaluated by the increase in [125I]casein digestion observed in the presence of plasminogen. The 52 K protein was estimated by analysing the released proteins on SDS-polyacrylamide gel electrophoresis. When the conditioned medium was chromatographed on concanavalin A-Sepharose, the 52 K protein was retained on the gel, but not the PA. The two proteins also appeared different on the basis of their competing efficiency in a radioimmunoassay developed to quantify the 52 K protein. An antiserum against human urokinase failed to immunoprecipitate the 52 K protein. Under our culture conditions estradiol increased 52 K, but not PA, production. These results clearly indicate that the estradiol-regulated 52 K protein is not a plasminogen activator.
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PMID:The estrogen-regulated 52 K protein adn plasminogen activators released by MCF7 cells are different. 653 16

Destruction of the extracellular matrix is often observed during tumor invasion, and proteolytic enzymes may participate actively in the degradation of matrix proteins. The present report elucidates the role of plasminogen in the degradation by tumor cells of an in vitro elaborated extracellular matrix. Matrices produced by rat smooth muscle cells in the presence of [3H]proline or [3H]fucose were used as substrates for human fibrosarcoma cells (HT-1080), mouse melanoma cells (B16F1), or human rhabdomyosarcoma cells (RD). All three cell lines degraded part of the glycoprotein compartment of the matrix. HT-1080 cells digested the matrices in a density-dependent manner, and while matrix glycoprotein degradation was plasminogen-dependent at the beginning of the experiment and at low cell densities, the zymogen was not essential for further glycoprotein digestion at high cell densities. Depletion of plasminogen from the growth medium resulted in a threefold reduction of matrix degradation by B16F1 cells showing a distinct plasminogen dependency at low cell numbers. RD cells digested only matrix glycoproteins, and this degradation was completely dependent on the presence of plasminogen at all cell densities. These results suggested that plasmin generated from plasminogen by a tumor cell-associated plasminogen activator may be most important for matrix hydrolysis at low cell densities, and while certain tumor cell lines showed a definite plasminogen-independent matrix degradation with increased cell numbers, other neoplastic cells hydrolyzed the matrix only in the presence of the zymogen at all cell densities.
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PMID:Role of plasminogen in matrix breakdown by neoplastic cells. 658 58

The expression of transformation parameters (inhibition of cell division during cell crowding, anchorage dependence, loss of fibrin clot retractile activity and secretion of plasminogen activator) was studied in a heterospecific cellular hybrid, made between established L(TK-) cells and the normal human MRC-5 cells. The hybrid nature of the cross was confirmed by the ability to incorporate [3H]-thymidine, by growth in selective HAT medium, by the identification of human chromosomes and by the expression on the surface of 100% of hybrid cells of a human glycoprotein, which is recognized by the 4F2 monoclonal antibody. The hybrid cultures showed cell cycle inhibition which became less stringent with increasing population doublings and the loss of human chromosomes. Fibrin clot retraction and anchorage dependence were absent in spite of the presence of many human chromosomes. The two properties were present or lost simultaneously in the normal parent cells and in the transformed parent or hybrid cells respectively. The human type of plasminogen activator was secreted even with very little human genetic material left, and a complete dissociation between fibrin clot retraction and production of plasminogen activator was observed. The data strengthen the hypothesis that transformation is a multistep process that involves complex genetic control and where cells progressively express different phenotypes and escape growth control.
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PMID:Comparison of fibrin clot retraction with other transformation parameters after hydridization of normal and established cell lines. 668 7

Fibronectin is a polymorphic glycoprotein of plasma, other body fluids and connective tissue, and it occurs in an insoluble and a soluble form. Insoluble fibronectin is found associated with basement membranes and in loose connective tissue matrix as well as in the pericellular matrix formed around cultured adherent cells, such as endothelial, fibroblastic and smooth muscle cells. In these positions fibronectin apparently functions as a substrate for cell attachment and as a scaffold for cell migration and movement. Soluble fibronectin, present e.g. in the circulation (300 micronm/ml) exhibits some important interations with other proteins. It is covalently cross-linked to fibrin during thrombus formation and binds to collagen. Fibronectin is released from platelets during their aggregation and soluble fibronectin potentiates the action of plasminogen activator. We have detected fibronectin in the sub-endothelium, in the matrix of smooth muscle cells of the media and in the adventitia of arteries. By using immunohistological techniques we have further found that fibronectin is prominent in atherosclerotic lesions of the intima, especially in developing fibrous plaques. Fibronectin was also prominent in experimentally induced atherosclerotic lesions. These findings suggest that fibronectin is an indicator of connective tissue formation in atherosclerotic processes and that the protein can have a role in their pathogenesis.
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PMID:Fibronectin and atherosclerosis. 693 42

Four human tumor cell lines were grown in direct contact with the extracellular matrix proteins which had previously been produced by cultured rat smooth muscle cells. The extracellular matrix contained glycoproteins, elastin, and collagen, and its digestion by the tumor cells was followed by the appearance of radioactive breakdown products in the supernatant medium. All four tumor lines tested digested glycoproteins present in the matrix, whereas human fibroblasts were inactive in glycoprotein digestion. The human fibrosarcoma cell line (HT1080) demonstrated elastolytic and collagenolytic activity in addition to a plasmin-induced hydrolysis of glycoproteins. Removal of glycoproteins from the matrix was necessary for the maximal digestion rate of elastin and collagen, and plasmin generation by the tumor cell plasminogen activator therefore played a pivotal role in the hydrolysis of all of the matrix components. The elastolytic and collagenolytic activities were localized to the plasma membrane since no matrix digestion occurred unless the tumor cells were grown in direct contact with the connective tissue proteins. These activities were not inhibited by a wide spectrum of protease inhibitors. The degradation of elastin and collagen required active protein synthesis suggesting a relatively short half-life for the degradative enzyme(s). These quantitative studies, in which tumor cells were grown in contact with a complex extracellular matrix possessing some of the characteristics of connective tissue, should have a bearing on tumor cell invasion.
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PMID:Destruction of extracellular matrices containing glycoproteins, elastin, and collagen by metastatic human tumor cells. 700 Mar 40


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