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

Primary cultures of renal cell carcinomas and of the corresponding normal adjacent kidney tissue from 6 patients were analyzed for the effects of exogenously added urokinase-type plasminogen activator on cell proliferation as compared to the effects of tissue type plasminogen activator, plasmin and dihydrocortisone. Cell proliferation was studied over a period of up to 5 days by measuring 3H-thymidine incorporation as well as cell viability and cell count; conditioned media of the cultures were also analyzed for their plasminogen activator and plasminogen activator inhibitor content. Addition of urokinase stimulated cell proliferation in a time and dose dependent fashion; after 3 days 3H-thymidine incorporation was significantly increased in malignant renal cells (188.3 +/- 28.7%), while it reached in normal renal cells approximately 130% of the 3H-thymidine incorporation of untreated cultures. Tissue-type plasminogen activator had no effect and plasmin decreased cell proliferation slightly while dihydrocortisone inhibited cell proliferation significantly (34.1 +/- 4.9%) in malignant cells. It is concluded that urokinase-type plasminogen activator itself exhibits a mitogenic effect also on primary cultures of renal cell carcinomas.
Carcinogenesis 1988 Nov
PMID:Mitogenic effect of urokinase on malignant and unaffected adjacent human renal cells. 318 Mar 47

In an attempt to understand the mechanism by which estrogens stimulate cell proliferation and mammary carcinogenesis, metastatic human breast cancer cell lines (MCF7, ZR75-1) were found to secrete a 52,000 dalton (52K) protein under estrogen stimulation. Following its purification to homogeneity, the 52K protein was identified as a secreted procathepsin-D-like aspartyl protease bearing mannose-6-phosphate signals. This precursor displays an in vitro autocrine mitogenic activity on estrogen-deprived MCF7 cells and is able to degrade basement membrane and proteoglycans following its autoactivation. The total protease (52K + 48K and 34K) was detected and assayed by monoclonal antibodies and was found to be highly concentrated in proliferative and cystic mastopathies. In breast cancer, its cytosolic concentration appears to be correlated more to tumor invasiveness than to hormone responsiveness. The mRNA of the 52K protease accumulates rapidly following estradiol treatment, as was shown by Northern blot analysis with cloned cDNA. The 52K cathepsin-D-like protease is the first example of a lysosomal protease induced by estrogens in cancer cells. Results obtained using different approaches suggest that two cysteinyl cathepsins are also related to cell transformation and invasiveness. It has been proposed that cathepsin-B is involved in breast cancer and metastatic melanoma, and its regulation by estrogen has been shown in the rat uterus. Cathepsin-L corresponds to the major excreted protein (MEP) whose synthesis and secretion are markedly increased by transformation of NIH 3T3 cells with Ki ras and are regulated by several growth factors. In addition to secreted autocrine growth factors and to other proteases (plasminogen activator, collagenase), lysosomal cathepsins may therefore play an important role in the process of tumor growth and invasion as long as their precursor is secreted abundantly.
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PMID:Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? 331 45

The acute effects of 12-O-tetradecanoylphorbol-13-acetate [(TPA) CAS: 56937-68-9], T-2 toxin (CAS: 21259-20-1), capsaicin (CAS: 404-86-4), cigarette smoke condensate (CSC), and ethanol (CAS: 3807-77-0) were examined in secondary cultured human esophageal epithelial cells in serum-free LHC-8 medium. Effects were evaluated by morphology and measurement of clonal growth rate (population doublings per day), cross-linked envelope (CLE) formation, and the enzymatic activities of ornithine decarboxylase (ODC) and plasminogen activator (PA). All compounds tested were inhibitory to clonal growth; concentrations causing 50% growth inhibition were estimated as 10 nM TPA, 6 nM T-2 toxin, 40 microM capsaicin, 8 micrograms CSC/ml, 540 mM ethanol, and 0.8 microgram CSC/ml with 220 mM ethanol. None of the compounds tested induced CLE formation, although calcium ionophore (A23187) could induce CLE in at least 60% of the cells. TPA (10 and 100 nM) decreased the ODC activity of cells, and capsaicin (100 microM) induced ODC by 220%. TPA (1-100 nM) and capsaicin (100 microM) also induced PA activity. Slight increases in ODC activity by CSC (10 micrograms/ml), CSC (1 microgram/ml) with ethanol, and T-2 toxin (1 nM) were observed, but PA activity was not affected by these compounds. The results indicated that the response of human esophageal epithelial cells to TPA is both similar to and different from that reported for human epidermal and bronchial cells in vitro. Enhancement of PA activity and decrease in ODC by TPA are found in all three human epithelial cell types. However, these changes are not associated in esophageal cells with increased CLE formation as reported in studies with the use of bronchial and epidermal epithelial cells. The results from these acute studies provide the basis for designing in vitro carcinogenesis investigations using these agents.
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PMID:Effects of tumor promoters and cocarcinogens on growth and differentiation of cultured human esophageal epithelial cells. 346 55

The purpose of this work was to study the interrelationship of proliferation and secretion of plasminogen activator (PA) and interferon (IFN) by murine macrophages. For induction of macrophage proliferation and secretion of PA, concanavalin A (Con A) was used. Secretion of IFN was induced by polyinosinic polycytidylic acid complex. The glucocorticoid dexamethasone acetate (DA) (10(-6)-10(9) M) inhibited Con A-stimulated secretion of PA and synthesis of DNA as evaluated by incorporation of [3H]thymidine. DA did not inhibit IFN induction. Preincubating macrophages with DA for 45 h reduced basal proliferation and secretion of PA but did not reduce responsiveness to Con A. Also retinoic acid, a modulator of carcinogenesis was used in inhibition studies because of its known antagonistic effects on lymphocyte mitogenesis. In macrophages a biphasic effect of retinoic acid (1 X 10(-5) - 5 X 10(-5)M) was found: (a) inhibition of DNA synthesis and secretion of PA during the first 45 h of incubation, and (b) enhancement of DNA synthesis (but not PA secretion) after 72 h. Secretion of IFN was not affected. It is suggested that secretion of PA but not IFN is linked to cell cycle traverse of macrophages.
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PMID:Regulation of plasminogen activator secretion, interferon induction and proliferation in murine macrophages. 618 80

Excretion of plasminogen activator from colonies of Syrian hamster embryo cells has been studied after sequential exposure of the cells to benzo[a]pyrene (3 days), and 12-O-tetradecanoyl-phorbol-13-acetate (3 days). The excretion of plasminogen activator was assayed using the fibrin/agarose overlay technique. The frequency of plasminogen activator-positive colonies was about two times higher for morphologically transformed colonies than for colonies with normal morphology growing on the same dish. Thus, 9% of the transformed colonies, compared to 4% of the colonies with normal morphology, gave clear zones of lysis in the fibrin/agarose overlay after 2 h of incubation. The frequency of plasminogen activator-positive colonies on untreated dishes was 2%. The addition of protease inhibitors strongly reduced the formation of clear zones of lysis, while they did not affect the frequency of morphologically transformed colonies. The data show that the expression of plasminogen activator is not an obligatory event in the process of morphological transformation.
Carcinogenesis 1982
PMID:Fibrinolytic activity and morphological transformation of hamster embryo cells. 628 79

Effects of teleocidin B, 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,7-dichlorodibenzo-p-dioxin (DCDD) on normal human bronchial epithelial cell cultures were assessed by quantitation of cellular morphology, clonal growth (population doublings per day), cross-linked envelope (CLE) formation and the enzymatic activities of aryl hydrocarbon hydroxylase (AHH), ornithine decarboxylase (ODC) and plasminogen activator (PA). Toxicity was assessed by clonal growth assays. Teleocidin B and TPA had similar effects on growth, morphology and enzyme activities. When the cells were incubated with TPA or teleocidin B at concentrations of 1-100 nM for 6 h, RNA synthesis was unaffected, but DNA synthesis decreased and squamous differentiation, marked by an increase in cell surface area and cross-linked envelope formation, was increased. TPA and teleocidin B also increased ODC activity in LHC-0 medium (a maintenance medium without epidermal growth factor) but caused a decrease of ODC activity in LHC-4 (a growth medium containing epidermal growth factor). Finally, TPA and teleocidin B each caused an increase of PA and a decrease of AHH activities in both media. Phorbol, a non-promoting analogue of TPA, had no effect on growth, morphology or biochemical assays. TCDD (100 nM) caused a 15% decrease in cell growth when cells were incubated in LHC-4, and this was accompanied by an increase in cell surface area, PA activity, and CLE formation. TCDD caused an increase in AHH and ODC activities when the cells were incubated in either LHC-0 or LHC-4 medium. DCDD did not alter cell growth, and its morphological and biochemical effects were similar to those of TCDD although less marked. In conclusion, results reported here are consistent with the hypothesis that an important property of some tumor promoters is their ability to induce terminal differentiation in normal, non-initiated epithelial cells.
Carcinogenesis 1984 Feb
PMID:Acute effects of 12-O-tetradecanoylphorbol-13-acetate, teleocidin B, or 2,3,7,8-tetrachlorodibenzo-p-dioxin on cultured normal human bronchial epithelial cells. 642 3

We have tested human fetal fibroblasts for development associated changes in DNA repair by utilizing nucleoid sedimentation as an assay for excision repair. Among skin fibroblasts the rate of excision repair was significantly higher in non-fetal cells than in fibroblasts derived from an 8 week fetus; this was evident by a delay in both the relaxation and the restoration of DNA supercoiling in nucleoids after irradiation. Skin fibroblasts derived at 12 week gestation were more repair proficient than those derived at 8 week gestation. However, they exhibited a somewhat lower rate of repair than non-fetal cells. The same fetal and non-fetal cells were also tested for induction of the protease plasminogen activator (PA) after u.v. irradiation. Enhancement of PA was higher in skin fibroblasts derived at 8 week than in those derived at 12 week gestation and was absent in non-fetal skin fibroblasts. These results are consistent with our previous findings that in human cells u.v. light-induced PA synthesis is correlated with reduced DNA repair capacity. Excision repair and PA inducibility were found to depend on tissue of origin in addition to gestational stage, as shown for skin and lung fibroblasts from the same 12 week fetus. Lung compared to skin fibroblasts exhibited lower repair rates and produced higher levels of PA after irradiation. The sedimentation velocity of nucleoids, prepared from unirradiated fibroblasts, in neutral sucrose gradients with or without ethidium bromide, indicated the presence of DNA strand breaks in fetal cells. It is proposed that reduced DNA repair in fetal cells may result from alterations in DNA supercoiling, and that persistent DNA strand breaks enhance transcription of PA gene(s).
Carcinogenesis 1984 Mar
PMID:DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light. 653 62

A series of phorbol esters stimulates prostaglandin E production from both resident and starch-induced mouse peritoneal macrophages. The relative potencies of these compounds parallel their abilities both to elevate macrophage plasminogen activator levels and to function as tumor promoters in a mouse skin carcinogenesis model. Low concentrations of antiinflammatory glucocorticoids, such as dexamethasone, inhibit the enhanced prostaglandin E synthesis as a result of 12-O-tetradecanoylphorbol-13-acetate action. The same glucocorticoids also inhibit the enhanced plasminogen activator production. On the basis of these observations, it is suggested that there might be a relationship between macrophage phospholipase activation and plasminogen activator synthesis. It is also suggested that these data might be providing insight into how 12-O-tetradecanoylphorbol-13-acetate and certain structural analogs elicit an inflammatory response and behave as tumor promoters in mouse skin.
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PMID:Stimulation of macrophage prostaglandin and neutral protease production by phorbol esters as a model for the induction of vascular changes associated with tumor promotion. 677 Sep 96

The plasminogen activation cascade is involved in carcinogenesis, invasion and metastasis. In this study plasminogen activators and their type 1 inhibitor were evaluated in colonic tissue from 19 patients with familial adenomatous polyposis coli, an inherited disorder characterised by the presence of thousands of adenomatous polyps in the colorectum which predispose to colorectal cancer. The conversion of normal-appearing colonic mucosa to neoplastic tissue in these patients was associated with an increase in urokinase-type plasminogen activator and plasminogen activator inhibitor type 1, accompanied by a decreased level of tissue-type plasminogen activator. These observations are essentially similar to those found in solitary adenomas and carcinomas of the colon, and illustrate the uniform involvement of the plasminogen activation system in colorectal carcinogenesis.
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PMID:Plasminogen activators and inhibitor type 1 in neoplastic colonic tissue from patients with familial adenomatous polyposis. 784 Oct 59

Human colorectal carcinogenesis has been shown previously to be associated with impressive changes in the tissue levels of plasminogen activators and their inhibitors, exemplified by an increase in the urokinase-type plasminogen activator (u-PA) and the inhibitors PAI-1 and PAI-2, and a decrease in tissue-type plasminogen activator (t-PA). In the present study we evaluated the prognostic significance of these parameters to the overall survival of patients with colorectal cancer, in conjunction with several major clinicopathological parameters like age, gender, differentiation grade, and Dukes' stage. Univariate analyses revealed that a low t-PA antigen level, low t-PA activity, and high u-PA/t-PA antigen ratio in normal mucosa and a high u-PA and PAI-2 antigen level in carcinomas are prognostic for a poor overall survival of patients with colorectal cancer. The prognostic value of t-PA antigen and activity in normal mucosa, the antigen ratio of u-PA in carcinoma (C) and t-PA in corresponding normal (N) mucosa [u-PA(C)/t-PA(N) antigen ratio], and PAI-2 antigen in carcinomas was found to be independent from clinicopathological parameters by multivariate analyses. These observations illustrate the clinical importance of the plasminogen activation cascade at the tissue level in colorectal cancer invasion, metastasis, and survival.
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PMID:Prognostic relevance of plasminogen activators and their inhibitors in colorectal cancer. 803 38


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