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 interaction of epidermal growth factor (EGF) with specific cell surface receptors initiates biochemical events in target cells which result in cellular proliferation and differentiation. In this report the regulation of extracellular-associated plasminogen activator (PA) production by EGF in human squamous cell carcinomas and its influence on tumor cell-mediated degradation of extracellular matrix (ECM) is described. The studies utilized the vulvar carcinoma cell line A431, which possesses an unusually large number of EGF receptors (EGF-Rs), and two A431 EGF-R expression variants (A5 and A7), which contain up to 20-fold fewer cell surface EGF-Rs. EGF enhanced the production of urokinase (u) PA activity by two- to threefold in A431 tumor cells, in a concentration-dependent manner, following a 24-h treatment, as determined by substrate hydrolysis assays, while no changes in tissue-type PA occurred. In contrast, A5 and A7 tumor cells failed to demonstrate such a response. Time course studies of the EGF-mediated induction of uPA activity in A431 tumor cells indicated that within 8 h after exposure to EGF, a twofold increase above basal untreated control levels was observed using the substrate hydrolysis assay. EGF increased the steady state levels of uPA mRNA threefold in A431 tumor cells following a 24-h treatment, while in contrast, no such response was observed in EGF-R variant tumor cells. In accord with an EGF enhancement of uPA mRNA levels in A431 tumor cells, a similar increase of two- to threefold in the de novo synthesis of [35S]methionine-radiolabeled uPA was observed by immunoprecipitation following EGF treatment, while no measurable increase was observed in the EGF-R tumor variants. A431 tumor cells progressively degraded [3H]glucosamine-radiolabeled bovine corneal subendothelial ECM in the presence of EGF, resulting in 8.7-, 4.3-, and 1.7-fold increases above untreated control values, after a 48-h exposure to 100, 10, and 1 ng/ml of EGF, respectively. In contrast, A5 and A7 tumor cells did not demonstrate an increase in ECM degradation in the presence of EGF, even though these tumor cells possessed the ability to degrade ECM in the absence of the growth factor. The observed increase in ECM degradation mediated by EGF in A431 tumor cells was dependent upon the presence of plasminogen and could be inhibited by an anticatalytic uPA monoclonal antibody.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation by epidermal growth factor of human squamous cell carcinoma plasminogen activator-mediated proteolysis of extracellular matrix. 249 75

Tumor necrosis factor-alpha (TNF-alpha) was found to induce type-1 plasminogen activator inhibitor (PAI-1) antigen in the human fibrosarcoma cell line HT-1080, and PAI-1 and urokinase-type plasminogen activator (u-PA) antigens in the human carcinoma cell line T-CAR1; tissue-type plasminogen activator (t-PA) antigen was not affected or slightly decreased. The effects in HT-1080 and T-CAR1 cells were preceded by increases in the cellular levels of the corresponding mRNAs. Cycloheximide caused an increase of PAI-1 mRNA in T-CAR1 cells, but not in HT-1080 cells; during this increase the relative abundance of the two PAI-1 mRNA species, of 2.3 kb and 3.4 kb, respectively, changed strongly in favor of the longer transcript. We conclude that TNF-alpha may affect proteolytic activity in the microenvironment of cells in malignant tumors by affecting gene expression of u-PA and PAI-1.
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PMID:Tumor necrosis factor-alpha regulates mRNA for urokinase-type plasminogen activator and type-1 plasminogen activator inhibitor in human neoplastic cell lines. 250 Nov 20

Four sub-lines (strain A, C, D, E) were isolated from a human lung giant cell carcinoma cell line (PLA-801) by the single cell cloning technique. The incidence of spontaneous metastasis was higher in strain D, moderate in strains A, E and lower in strain C after they were inoculated subcutaneously into the nude mice. The lung and lymph-nodes were the major target organs of metastasis. Morphological studies (light microscope, electron microscope and immunohistochemistry) showed that the cytoplasm of metastatic tumor cells was rich in microfilament and positive for Vimentin. The results strongly support the theory on tumor cell heterogenicity. In addition, these clones, especially strains D and C, could be an ideal model for the study of tumor metastasis.
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PMID:[Spontaneous metastasis of clonal cell subpopulations of human lung giant cell carcinoma after subcutaneous inoculation in nude mice]. 255 Jan 96

Several human lung tumor cell lines derived from large cell, squamous cell, and small cell carcinomas, as well as from mesotheliomas of the lung have been investigated for their gene expression and secretion of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitors 1 and 2. All bronchogenic non-small cell carcinoma-derived cell lines studied could produce either plasminogen activators, their inhibitors, or both components, whereas in small cell lung carcinoma cell lines and cell lines derived from mesothelioma of the lung, no substantial amounts of any of these substances were synthesized. In detail, a large cell carcinoma-derived cell line, LCLC 97TM1, constitutively secreted large amounts of plasminogen activator. Northern blot analysis revealed RNA specific for u-PA and t-PA. Another large cell carcinoma-derived cell line, LCLC 103H, secreted smaller amounts of plasminogen activator and, additionally, plasminogen activator inhibitor. Specific mRNAs for u-PA and plasminogen activator inhibitors 1 and 2 were found in this cell line. In contrast, squamous cell carcinoma-derived cell lines secreted plasminogen activator only after treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate; enhanced levels of u-PA, t-PA, and plasminogen activator inhibitor 1 mRNAs could then be demonstrated. The different expression of the plasminogen activator enzyme system distinguishes cell lines derived of non-small cell lung carcinoma from those of small cell lung carcinoma and may also reflect significant differences in the biological behavior of these tumor types.
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PMID:Synthesis and secretion of plasminogen activators and plasminogen activator inhibitors in cell lines of different groups of human lung tumors. 255 56

From 9 female patients suffering from carcinoma cervicis (8 women with a stage Ib, 1 woman with a stage IIa carcinoma) blood was taken immediately from the ovarian veins and a cubital vein after laparotomy on the occasion of a surgical intervention according to Wertheim-Held. Fibrinogen was isolated from plasmas by affinity chromatography at fibrin monomer Sepharose and characterized by SDS-PAGE. With one exception proteolytically changed fibrinogens could be demonstrated in all plasmas. In 7 cases the fibrinogens from ovarian blood were more degraded than fibrinogen derivates in the blood obtained from cubital veins. It is assumed that the proteinase and/or plasminogen activator activities of tumor tissues are of importance for the observed proteolytic effects.
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PMID:[Proteolytic changes in plasma fibrinogen from ovarian venous blood in patients with cervix cancer]. 258 74

In order to characterize further the previously observed induction of a highly metastatic phenotype in mouse bladder carcinoma cells by Ha-ras transfection, we studied production of plasminogen activator, in vitro invasiveness, and the potential for lung colonization of these cells. The parent carcinoma cells produced predominantly tissue-type plasminogen activator. Out of 13 clones of ras-transfected cells tested, 8 secreted quantitatively elevated levels of plasminogen activator (up to 3.5-fold) as compared to the control transfectants. The plasminogen activator activity in cell lysates was maximally increased 3-fold, the surface-associated activity increased 2.5-fold. The secreted plasminogen activator of cloned ras-transfected cells was characterized to be predominantly of the urokinase type (71.3% compared to 20.5% with the parental BL cells). Thus, in addition to the quantitative augmentation of plasminogen activator production and secretion in a large fraction of the ras-transfected cell population, a significant qualitative shift from tissue-type to urokinase-type has been observed. In addition, ras-transfection augmented the capacity of the cells for invasion into Matrigel in a double-filter in vitro assay as well as their ability to colonize the lungs of syngeneic animals. These malignant properties of the transfected cells might be responsible for their highly metastatic behaviour induced by ras transfection.
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PMID:Induction of urokinase activity and malignant phenotype in bladder carcinoma cells after transfection of the activated Ha-ras oncogene. 265 32

Plasminogen activator activity was demonstrated in two carcinoma cell lines: A549 cells derived from a human alveolar epithelial carcinoma; and ZHC cells derived from a rat hepatoma. Both cells had intracellular plasminogen activator activity throughout their cell cycles and in each case this activity reached a maximum. For A549 cells the maximal activity took place either during the G2 phase or in the course of the S to G2 transition, suggesting that plasminogen activator might play a role in cell division. For ZHC cells, the maximal activity occurred at the start of the S phase, suggesting that in these cells plasminogen activator might be involved in DNA replication.
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PMID:Cell cycle-specific variation of intracellular plasminogen activator activity in cultured human alveolar epithelial carcinoma and rat hepatoma cells. 275 14

Controlled-release polymeric needle devices containing adriamycin HCL (ADH) were investigated by an in vitro dissolution study in normal saline solution and an in vivo antitumor activity in C3H mice bearing mammary carcinoma and nude mice bearing brain tumor. HPMC was used as a release rate regulator. The ADH released from needle devices was controlled by the types of polymer used and the addition of HPMC. EVA needle devices exhibit a zero order release behavior better than that of PLA needle devices. Tumor growth was markedly inhibited by treatment with needle devices after locally inserted into the solid tumor. The rank of antitumor activity of the needle devices is EVA greater than PLA greater than EVA-HPMC greater than PLA-HPMC. No significant changes in body weight of mice after treatment were found in treated groups as compared to controlled groups. The preliminary results of our study suggest that needle device dosage form shows a controlled release behavior and may be applicable as a drug carrier for delivery of antitumor drug in cancer chemotherapy.
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PMID:Tumoricidal effect of controlled-release polymeric needle devices containing adriamycin HCl in tumor-bearing mice. 277 78

In cultures of the human mammary carcinoma-derived cell line MDA-MB-231, plasminogen activator (PA) activity was reduced substantially following treatment with the glucocorticoid dexamethasone. These cells produced urokinase-type PA (u-PA) and tissue-type PA (t-PA), and both enzymes were decreased in dexamethasone-treated cultures. The drop in u-PA activity was associated with a decrease in the synthesis of single-chain pro-u-PA and in the concentration of u-PA messenger RNA; however, the decrease in u-PA activity was more extensive than could be accounted for by inhibition of enzyme synthesis only, suggesting that postsynthetic events were also involved. The comparatively small dexamethasone-induced decrease in t-PA activity was not associated with a change in the concentration of t-PA messenger RNA. Hence, the two PA genes are differentially regulated by the same hormone. MDA-MB-231 cells also produced a PA-specific inhibitor related to that produced by bovine aortic endothelial cells (PAI-1). This inhibitor was present in two forms: one functionally active, and the other which required activation by sodium dodecyl sulfate; both forms were increased in cultures exposed to dexamethasone. Thus, glucocorticoid-induced inhibition of PA activity in these cells results from a decrease in u-PA synthesis and a concomitant increase in the production of a PA inhibitor.
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PMID:Glucocorticoid modulation of plasminogen activators and of one of their inhibitors in the human mammary carcinoma cell line MDA-MB-231. 309 8

Changes in the plasma levels of components of the fibrinolytic system have been investigated in 80 patients suffering from gastrointestinal carcinomas. Urokinase antigen (RIA), tissue-type plasminogen activator antigen (ELISA) and plasminogen activator inhibitor (functional assay) were determined. Patients with pancreatic and colorectal carcinoma and metastases as well as those without metastases revealed significantly increased plasma urokinase levels. Those with gall bladder or gastric carcinoma did not show significantly elevated urokinase antigen levels compared to age-matched controls. Determination of tissue-type plasminogen activator antigen in all four carcinoma groups did not reveal significant differences when compared to an age-matched healthy control group. The concentrations of plasminogen activator inhibitor were significantly increased in all carcinoma groups; there being no differences between the patient groups with or without metastases. No correlations between the different parameters of the fibrinolytic system could be obtained.
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PMID:Pattern of fibrinolytic parameters in patients with gastrointestinal carcinomas. 310 63


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