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)

Component levels of the fibrinolysin system in the plasma and ascitic fluid of Swiss mice bearing Ehrlich ascites tumor cells were determined during a 15-day tumor growth time phase. During tumor growth, the concentration of plasminogen in the ascitic fluid decreased inversely to the total packed cell volume. Free plasmin was not present in the ascitic fluid nor was there any measurable plasminogen activator activity. Both antiplasmin activity and fibrinogen levels present in the fluid decreased during tumor growth. The nuclear and mitochondrial-microsomal subcellular fractions of the tumor cell exhibited plasminogen activator activity. No significant changes in the above parameters occurred in the plasma during the tumor growth period we studied.
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PMID:Proteases during the growth of Ehrlich ascites tumor. I. The fibrinolysin system. 12 66

This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF). Low concentrations of retinoic acid (RA) (10(-6)-10(-10) M) and the retinoids stimulated PA synthesis in CEF; the maximal stimulation achieved, 9--10 fold, was somewhat lower than that obtained with optimal concentrations of the potent tumor promoter phorbol myristate acetate (PMA). This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP. In inducing and/or stimulating PA production, the effects of RA and sarcoma virus transformation were synergistic rather than additive. Analogous synergism was observed between RA and PMA, but only at suboptimal concentrations of the latter. RA did not affect PA production in normal or transformed cultures maximally stimulated by PMA. These findings may help to elucidate the role of retinoids in promoting tumor growth, tissue remodeling and teratogenesis.
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PMID:Plasminogen activator in chick fibroblasts: induction of synthesis by retinoic acid; synergism with viral transformation and phorbol ester. 21 37

Seven clones were isolated from the HT1080 human fibrosarcoma cell line using a fibrinagarose overlay technique. Three of these clones induced lysis of the fibrin overlay, whereas four did not. The extracellular and intracellular levels of protease were then measured using 125I-fibrin plates incubated with acid-treated human serum. The extracellular protease can be directly assayed in the medium from cells incubated with 10% fetal calf serum. Although there were large differences in the amounts of protease secreted by these two sets of clones, the intracellular levels of protease were similar. No significant differences were found between the abilities of the cells to grow in soft agar or as tumors in immunosuppressed hamsters. However, cells grown from tumors derived from all the low secretors of protease showed an increase in the amount of protease secreted. It appeared, therefore, that the secretion of protease might be selected for or induced during tumor growth. Further detailed studies with one of the low secreting clones (clone E) suggested an inductive rather than a selective mechanism for this increase in extracellular plasminogen activator.
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PMID:Fibrinolytic activity in a human fibrosarcoma cell line and evidence for the induction of plasminogen activator secretion during tumor formation. 118 4

Recent reports have suggested that tissue-type plasminogen activator activity is regulated by estrogen in 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma type I cells but is not necessarily regulated by estrogen in type II mammary carcinoma cells. We have compared the biological features of these two types of mammary carcinoma cells and have found that, although there is no difference in estrogen receptor content between these two cell types, the plasminogen activator activity markedly differs. Tissue-type plasminogen activator activity is significantly higher in type I carcinoma than in type II carcinoma, urokinase-type activity is significantly higher in type II carcinoma than in type I carcinoma. When these two types were compared in terms of rate of tumor growth, type II carcinomas clearly showed more rapid growth than type I carcinomas. Survival studies showed significantly shorter survival of type II tumor-bearing rats compared with type I tumor-bearing rats. Furthermore, type II carcinomas contained a greater proportion of aneuploid cells than type I carcinomas. These results suggest that type II carcinoma cells, in which estrogen is unable to regulate tissue-type plasminogen activator activity, are considered to be of a higher grade of malignancy than type I carcinoma cells.
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PMID:Demonstration of a possible link between high grade malignancy in dimethylbenz[a]anthracene-induced rat mammary carcinoma and increased urokinase plasminogen activator content. 152 Sep 14

Liarozole reduced tumor growth in the androgen-dependent Dunning-G and the androgen-independent Dunning MatLu rat prostate carcinoma models as well as in patients with metastatic prostate cancer who had relapsed after orchiectomy. In vitro, liarozole did not have cytostatic properties, as measured by cell proliferation in breast MCF-7 and prostate DU145 and LNCaP carcinoma cell lines. It did not alter the metabolism of labeled testosterone i.e. the 5 alpha-reductase in cultured rat prostatic cells. In mouse F9 teratocarcinoma cells liarozole did not show any retinoid-like properties but enhanced the plasminogen activator production induced by retinoic acid. Furthermore, liarozole and retinoic acid similarly reduced the growth of the androgen-dependent Dunning-G tumor in nude mice and inhibited tumor promotion elicited by phorbol ester in mouse skin. These data have raised the hypothesis that the antitumoral properties of liarozole may be related to inhibition of retinoic acid degradation, catalyzed by a P-450-dependent enzyme that is blocked by the drug.
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PMID:Experimental studies with liarozole (R 75,251): an antitumoral agent which inhibits retinoic acid breakdown. 152 60

Transforming growth factor-beta (TGF-beta) is a potent mediator of cell proliferation and extracellular matrix formation, depending on the cell type and the physiological conditions. TGF-beta is usually secreted in a "latent" complex that needs activation before it can exert its effects. Several observations correlate increased expression of TGF-beta 1 with tumorigenesis. To evaluate the physiological relevance of increased TGF-beta 1 synthesis in tumor cells we established cell clones overexpressing TGF-beta 1 and observed the resulting physiological changes in TGF-beta overproducing cells in vitro and in vivo. As a model system we used the human E1A-transformed 293 tumor cells, which are insensitive to the direct growth modulatory effects of TGF-beta. The selection of this cell line allows an assessment of physiological alterations independent of TGF-beta induced proliferative changes. The use of two TGF-beta 1 expression vectors containing either the natural or a modified TGF-beta 1 precursor cDNA permitted the establishment of separate 293 cell lines overexpressing latent or active TGF-beta. Comparison of the resulting changes in glycolytic rate, adhesiveness and integrin and plasminogen activator expression established that, in vitro, both types of clones behaved similarly, indicating that expression of latent TGF-beta induces autocrine changes in the tumor cells and thus suggesting that some level of cell-associated activation occurs. TGF-beta overexpression resulted in an increased metabolic rate due to enhanced glycolysis, a property long associated with tumor cells. This increased glycolysis was not associated with altered proliferation. Cells overexpressing TGF-beta also displayed enhanced fibronectin mRNA and plasminogen activator synthesis and increased adhesiveness in vitro. They showed enhanced survival when plated sparsely on plastic in the absence of serum, and attached more readily to laminin. In addition, synthesis of several beta 1 integrins, in particular the alpha 1/beta 1, alpha 2/beta 1, and alpha 3/beta 1, all of which recognize laminin, were enhanced. Finally, cells overexpressing active TGF-beta, but not latent TGF-beta, also showed increased tumorigenicity in nude mice. Thus, an increase in endogenous TGF-beta synthesis confers several proliferation-independent phenotypic changes which may be of significance for the survival of the tumor cell inoculum or its subsequent growth, and for tumor formation and development. In the case of cells expressing active TGF-beta, the release of active TGF-beta into the vicinity of the tumor cells may also result in a more hospitable environment for tumor growth.
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PMID:Altered metabolic and adhesive properties and increased tumorigenesis associated with increased expression of transforming growth factor beta 1. 163 53

Herpes simplex virus type 2-transformed hamster embryo fibroblasts (333-8-9 cells) produce increased plasminogen activator (PA) compared with normal hamster cells. These cells produce undifferentiated fibrosarcomas at the inoculation site in newborn hamsters, and metastasize to the lungs. Using a direct PA assay, in which 125I-labeled plasminogen is cleaved, the optimum pH and osmolarity for detection of the 333-8-9 extracellular PA were pH 8.9 and approximately 150 mOsmol. Secretion of enzyme did not vary significantly on a per cell basis over cell densities from 0.1 to 8.0 X 10(7) cells/T-75 cm2 flask. This assay demonstrates that the 333-8-9 cells produce at least 20-fold greater levels of PA than normal cell counterparts. Based on the molecular weight (50-58 kDa) of secreted 333-8-9 cells PA and lack of fibrin stimulation, we conclude that it is a urokinase type PA. Subclonal lines of the 333-8-9 cells, selected for an increased PA phenotype were stable in culture, more tumorigenic and probably more metastatic. Correlation of these two events was examined by passaging 333-8-9 cells in vivo to select for greater tumorigenic potential and then determining the production of PA by the in vivo-derived sublines. The metastatic potential of the resulting cells was heterogeneous. Increased PA production upon increased passage in vivo did not always occur, whether the cells were passaged as subcutaneous tumors or as ascites tumors. Thus, while enzyme production correlated with tumorigenicity when selecting cells for an increased protease phenotype, this correlation was not observed when selecting for in vivo tumorigenicity. The results suggest that increased ability to make PA represents only one of multiple selective advantages for tumor growth.
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PMID:Phenotypic properties of herpesvirus-transformed cells with high tumorigenic and metastatic ability. 215 88

Affinity-purified polyclonal rabbit antibodies prepared against recombinant basic fibroblast growth factor (bFGF) neutralized the ability of bFGF to stimulate plasminogen activator (PA) production and endothelial cell migration in vitro. After iodination and intraperitoneal injection of the antibodies in mice, approximately 76% of the maximum circulating level of 125I-anti-bFGF antibodies (AF) was found as intact IgG after 24 hr. Furthermore, the circulating 125I-AF retained the ability to bind bFGF. Studies were performed to determine whether the growth of three different murine tumors (CT26, EHS, or B16/BL6) could be inhibited with affinity-purified neutralizing antibodies against bFGF. Tumors were injected subcutaneously in syngeneic mice, and neutralizing antibodies against bFGF were injected daily into the peritoneum. All studies, which varied in tumor burden, antibody dose, and study length, indicated that neutralizing antibodies against bFGF had no effect on tumor size, tumor growth, or tumor histology.
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PMID:Studies on the role of basic fibroblast growth factor in vivo: inability of neutralizing antibodies to block tumor growth. 219 45

The effects of protease inhibitors(PI), t-AMCHA, gabexate, aprotinin and heparin on the growth of mouse MM2 ascites tumor (MAT) and on several components of fibrinolysis were studied. The drugs were administered intraperitoneally one time daily for 12 days, one day after the tumor transplant. The volumes of ascites, total packed cell volume (TPCV) and fibrinolytic parameters (FDP, whole plasmin, plasminogen activator (PA)) were measured on the 8, 10 and 12th days of therapy. Fibrinolytic activity was assayed by the lysin sepharose affinity chromatography-radio caseinolytic method. Fibrinolytic activity in the ascites increased during the tumor growth. The ascites accumulation as well as levels of FDP, whole plasmin and PA in the drug treated group were significantly decreased when compared to the control group. In these drug-treated groups, MAT cells agglutinated in the abdominal cavity, but in contrast to this, no agglutination was observed in the control group. It was uncertain whether PI directly inhibited tumor growth. The fact that PI inhibited the ascites accumulation and also decreased fibrinolytic activity suggest the involvement of protease in the neoplastic process and indicates another therapeutic approach to malignant ascites tumors.
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PMID:[Studies on fibrinolysis and ascites accumulation associated with peritonitis carcinomatosa--effects of protease inhibitors (PI) on MM2 ascites tumor growth, ascites accumulation and fibrinolysis]. 242 22

A body of evidence has suggested that hormones which modulate plasminogen activator production by cultured tumor explants in vitro may have a qualitatively comparable effect on the growth of the same tumors in vivo. As a test of this correlation and to explore its potential for predicting the in vivo response of tumors to hormones, we have studied here the effect of hydrocortisone on the growth of primary and first generation transplants of mouse mammary tumor virus-determined mammary tumors in BALB/c X DBA/8 F1 (hereafter called CD8F1) mice; hydrocortisone had been found previously to inhibit plasminogen activator production by explants of these tumors. The results were: (a) hydrocortisone reversibly blocked the growth of palpable primary tumors; growth resumed at control rates following withdrawal of exogenous hormone; (b) hydrocortisone inhibited the growth of first-generation tumor transplants when administered either before or after the appearance of palpable tumors; (c) pretreatment with hydrocortisone both delayed the appearance of primary tumors and greatly reduced tumor incidence in susceptible mice; a substantial part of the decrease in tumor incidence was apparently irreversible; (d) hydrocortisone reduction of tumor growth was accompanied by inhibition of tumor plasminogen activator content, and these effects displayed a similar dose dependence (enzyme content of tumor lysates was measured by the 125I-fibrin plate assay); the enzyme present in control and hormone-treated tumors was predominantly of the urokinase type. These findings suggest that plasminogen activator production and mammary tumor growth in CD8F1 mice are coordinately regulated and thus encourage the view that plasminogen activator might be useful as an in vitro marker for predicting the in vivo response of tumors to hormones.
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PMID:Coordinate inhibition of plasminogen activator and tumor growth by hydrocortisone in mouse mammary carcinoma. 298 48


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