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

We have examined conditioned medium (CM) from cultures of normal rat mammary epithelial (RME) cells for growth factor activity on fresh RME cell cultures. RME cell-derived CM contained potent growth inhibitory activity toward fresh RME cell cultures when the medium was acidified by dialysis against 1% acetic acid prior to concentration. Dialysis of the CM at neutral pH resulted in CM that had growth stimulatory activity and no inhibitory activity. The acid-activated growth inhibitor was heat and acid stable, protease sensitive, and eluted from a Bio-Gel p60 column with a peak of activity in the 28 kDa range. Incubation of the acidified-concentrated CM with neutralizing antiserum (affinity purified IgG) against transforming growth factor (TGF)-beta completely abolished the inhibitory activity of the CM. Furthermore, RME cell growth in the presence of the growth inhibitor plus TGF-beta antiserum was greater than that observed in growth medium alone. Subsequent experiments demonstrated that addition of TGF-beta antiserum alone to serum-free medium enhanced RME cell growth, whereas addition of nonimmune IgG was without effect even at 25-fold higher concentrations. Zymographic analysis of RME-CM revealed the presence of plasminogen activator proteases that may mediate the partial activation of the latent growth factor. These results indicate that normal RME cells secrete a latent TGF-beta-like growth factor into conditioned medium. Furthermore, the results indicate that some of the latent growth factor is activated in situ and contributes to the growth potential of the cells in primary culture in an autocrine manner.
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PMID:Secretion of a TGF-beta-like growth inhibitor by normal rat mammary epithelial cells in vitro. 229 17

After incubation with human serum or plasma, 125I-basic fibroblast growth factor (bFGF) (molecular mass 18.5 kDa) exhibits molecular mass forms greater than 200 kDa as determined by nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. These high molecular mass forms of bFGF are immunoprecipitable with antiserum raised against alpha 2-macroglobulin (alpha 2M). Purified alpha 2M and 125I-bFGF form a covalent complex in a specific, saturable manner. Excess unlabeled bFGF competes with 125I-bFGF for complex formation. Complex formation is complete after 4 h and is inhibited by pretreating alpha 2M with dithiothreitol, iodoacetamide, iodoacetic acid, and N-ethylmaleimide. The complex is resistant to acidic conditions and denaturants such as urea. Heparin, which binds bFGF, has no effect on complex formation. Methylamine, which blocks protease binding to alpha 2M, increases the amount of 125I-bFGF that can be bound 2-fold. Plasmin and trypsin treatment of alpha 2M has no effect on 125I-bFGF binding. The ability of growth factors to compete for binding is specific, as aFGF and TGF-beta compete for binding to alpha 2M, whereas platelet-derived growth factor does not. 125I-bFGF.alpha 2M complexes do not bind to low affinity bFGF binding sites and bind poorly to high affinity bFGF binding sites on BHK-21 cells. In addition, 125I-bFGF bound to alpha 2M has decreased ability to stimulate plasminogen activator production in bovine capillary epithelial cells.
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PMID:Alpha 2-macroglobulin is a binding protein for basic fibroblast growth factor. 246 67

Type beta transforming growth factor (TGF-beta) was shown to be the serum factor responsible for inducing normal human bronchial epithelial (NHBE) cells to undergo squamous differentiation. NHBE cells were shown to have high-affinity receptors for TGF-beta. TGF-beta induced the following markers of terminal squamous differentiation in NHBE cells: (i) increase in Ca ionophore-induced formation of crosslinked envelopes; (ii) increase in extracellular activity of plasminogen activator; (iii) irreversible inhibition of DNA synthesis; (iv) decrease in clonal growth rate; and (v) increase in cell surface area. The IgG fraction of anti-TGF-beta antiserum prevented both the inhibition of DNA synthesis and the induction of differentiation by either TGF-beta or whole blood-derived serum. Therefore, TGF-beta is the primary differentiation-inducing factor in serum for NHBE cells. In contrast, TGF-beta did not inhibit DNA synthesis of human lung carcinoma cells even though the cells possess comparable numbers of TGF-beta receptors with similar affinities for the factor. Epinephrine antagonized the TGF-beta-induced inhibition of DNA synthesis and squamous differentiation of NHBE cells. Although epinephrine increased the cyclic AMP levels in NHBE cells, TGF-beta did not alter the intracellular level in NHBE cells in either the presence or absence of epinephrine. Therefore, epinephrine and TGF-beta appear to affect different intracellular pathways that control growth and differentiation processes of NHBE cells.
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PMID:Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. 287 53

Phorbol and eight of its derivatives were investigated for their ability to stimulate the synthesis of the enzyme plasminogen activator in cultured chick embryo fibroblasts and to aggregate human blood platelets and have been assayed for tumor, promoting and skin, irritant activities. Over a range of concentrations, elevation in the levels of plasminogen activator activity induced by phorbol derivatives correlates well with their promoting and irritant properties. In the platelet aggregation assay however, the parallelism between the activities measured in different biological assays was less complete. While strong promoters, such as TPA, are potent aggregating agents, and weak promoters, such as PDA, are poor or ineffective inducers of aggregation, two derivatives, PDD and PDB, deviate from this general result. Platelets must be exposed to PDD in relatively high concentrations before they will aggregate, and PDB was found to be the most potent aggregating agent of all the derivatives tested.
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PMID:Plasminogen activator induction and platelet aggregation by phorbol and some of its derivatives: correlation with skin irritancy and tumor-promoting activity. 719 86

Basic fibroblast growth factor (bFGF; FGF-2) lacks a signal sequence and thus is not secreted by classical pathways. It has been speculated that one mode of bFGF release may be injury, either sublethal or lethal; and, transient disruption of the plasma membrane has been shown to release bFGF [Muthukrihnan et al. (1991): J Cell Physiol 148:1-16]. This observation has led to the concept of bFGF as a "wound hormone," involved in tissue integrity and repair. Findings of elevated bFGF following injury in vivo support this concept. Using an in vitro model, we have examined the regulation of bFGF gene expression following its release by sublethal injury. Analysis of bFGF protein by ELISA revealed that scraping subconfluent bovine aortic EC (BAE) released up to 80% of their bFGF. Following scraping, there was a 4- to 10-fold increase in the steady state level of bFGF mRNA, which reached a maximum at 2-3 h. There was a parallel increase in protein so that by 6 h after the scrape-induced release, bFGF levels were restored to those measured prior to scraping. Since bFGF has been reported to induce its own expression, we hypothesized that the released bFGF might be responsible for the increase in bFGF mRNA. However, inclusion of neutralizing antibodies against bFGF had a negligible effect on the scrape-induced increase in bFGF mRNA levels. Because of the important role of transforming growth factor type-beta 1 (TGF-beta 1), the plasminogen/plasminogen activator system, and thrombin in wound healing, we investigated their potential contributions to the increase in bFGF expression. Addition of anti-TGF-beta 1 antibodies, plasminogen activator inhibitor-1 (PAI-1), or the thrombin inhibitory combination of heparin and anti-thrombin III (AT III) to the cells at the time of scraping blocked about 50% of the increase in bFGF mRNA; the effects of these agents were not additive. The suppression of bFGF mRNA was associated with a proportional reduction in bFGF protein. Inclusion of the antagonists for 2 h at the time of scraping led to reduced cell proliferation, suggesting that cell-associated bFGF may be required for recovery and growth. Finally, studies to characterize the molecular mechanisms underlying the increased bFGF mRNA following sublethal injury revealed an increase in the transcriptional activation of bFGF gene. These results indicate that in spite of the fact that bFGF is not a secreted protein, levels of bFGF in the cell are tightly regulated. Furthermore, these findings suggest a role for bFGF in recovery from cell injury.
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PMID:Regulation of basic fibroblast growth factor (bFGF) gene and protein expression following its release from sublethally injured endothelial cells. 759 55

It has been shown that some types of tumour cells produce activated transforming growth factor beta-1 (TGF-beta 1). However, the mechanism for the activation of TGF-beta 1 derived from tumour cells has not been fully elucidated. The present study was undertaken to characterise an activator of latent TGF-beta 1 secreted from a human gastric cancer cell line, KATO-III. Western blot analyses using antibodies for TGF-beta 1, latency associated peptide (LAP) and latent TGF-beta 1-binding protein (LTBP) revealed that, in the cell lysate of KATO-III, TGF-beta 1 protein was expressed as a small latent complex of TGF-beta 1 and LAP. This was also confirmed by a gel chromatographic analysis of the cell lysate obtained from KATO-III. A 2.5 kb transcript of TGF-beta 1 mRNA was detected in KATO-III cells by Northern blot analysis. A gel chromatographic analysis of the conditioned medium from KATO-III cells revealed, in addition to the active form of TGF-beta 1, a factor which activated latent TGF-beta 1 from NRK-49F cells at fractions near a molecular size of 65,000. This factor was inactivated by heat (100 degrees C), acidification, trypsin and serine protease inhibitors. TGF-beta 1 activity in KATO-III cell lysate was not detected in the untreated state, but potent TGF-beta 1 activity was detected after acid treatment. These results suggest that KATO-III releases not only a latent TGF-beta 1 complex but also a type of serine protease, different from plasmin, plasminogen activator, cathepsin D, endoglycosidase F or sialidase, which activates the latent TGF-beta 1 complex as effectively as acid treatment.
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PMID:Identification of a transforming growth factor beta-1 activator derived from a human gastric cancer cell line. 766 80

Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in the positive regulation of angiogenesis in vivo, whereas it inhibits the proliferation of endothelial cells in vitro. To reconcile these apparently contradictory effects, we have investigated the effect of TGF-beta 1 on bovine aortic endothelial cells that exhibit spontaneous angiogenesis in vitro. We show that concentrations of TGF-beta 1 which stimulate proliferation of cells that form endothelial cords and/or tubes inhibit proliferation of the same cells grown at subconfluent densities. An increase in cell number of 35% over control cultures was achieved with 0.5 ng TGF-beta 1/ml. The proliferative effect was blocked by antibodies against TGF-beta. Immunological detection of BrdU-labeled nuclei revealed an increase greater than 220% in cells treated with TGF-beta 1. Moreover, a population of cells within the cords appeared to be a selective target for this cytokine. The stimulatory effect was not restricted to bovine aortic endothelial cells, as similar results were obtained with endothelial cells derived from rat microvessels. Significant levels of active TGF-beta 1 were detected in cultures containing cords/tubes, whereas only latent TGF-beta 1 was detected in subconfluent cultures. We show further that endothelial cells exhibiting angiogenesis in vitro secrete plasminogen activator, an enzyme that regulates activation of TGF-beta. The major increases in mRNA transcripts for extracellular matrix proteins that are typically associated with TGF-beta 1 were not seen in cells exhibiting angiogenesis in vitro. Since the formation of tubular networks requires both invasion and proliferation, we propose that TGF-beta 1 is a major morphoregulatory factor in angiogenesis that specifically controls endothelial cell proliferation and extracellular matrix turnover.
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PMID:Endothelial cells exhibiting angiogenesis in vitro proliferate in response to TGF-beta 1. 769 28

We investigated immunohistochemically the localization of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), plasmin inhibitor (PI), and transforming growth factor-beta (TGA-beta) in tissue sections to examine the relationships between their localization and local invasiveness, tumor size and cervical lymph node metastasis of head and neck squamous cell carcinomas (SCCs). In invasive carcinomas, u-PA, PAI-1 and PI were stained stronger in carcinoma cells than in surrounding connective tissues or normal epithelial cells. However, no relationship was found between cell invasiveness and the localization of t-PA and TGF-beta in invasive SCCs. The expression of these factors was not related to cervical lymph node metastasis or the size of head and neck SCCs. These results suggest a disorder of the fibrinolytic systems of carcinoma cells, and that u-PA play a part in the invasion of head and neck SCCs by degenerating connective tissue.
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PMID:[Immunohistological study of fibrinolytic factors of head and neck squamous cell carcinomas]. 770 77

We characterized the human KW cell line to investigate whether it can serve as a model to study uterine muscle physiology in vitro. KW cells stained (a) positive for vimentin, smooth-muscle-specific alpha actin, tissue-type plasminogen activator (tPA), urokinase-type PA (uPA), uPA receptor, PA inhibitor 1, latent transforming growth factor beta 1 (latent TGF-beta 1) and 17 beta-hydroxysteroid dehydrogenase type I, and (b) negative for desmin, endoglin and cytokeratin 19. Insulin-like growth factor I, epidermal growth factor and platelet-derived growth factor stimulated the DNA synthesis in KW cells in a dose-dependent manner. Therefore, KW cells express a phenotype compatible with human uterine muscle cells. Hence, they can serve as a model to study uterine muscle physiology in vitro.
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PMID:Characterization of KW smooth muscle-like human myometrial cells. 784 22

Tube formation in collagen gel was induced in human omental microvascular endothelial (HOME) cells in the presence of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). TGF-alpha enhanced the expression of the tissue type plasminogen activator (t-PA) gene, whereas TGF-beta increased the expression of the PA inhibitor-1 (PAI-1) gene and inhibited that of the t-PA gene. TGF-beta inhibited the tube formation of HOME cells in type I collagen gel that was enhanced in response to TGF-alpha. We have recently established an angiogenesis model in vitro in which vascular endothelial cells on type I collagen gel in an inner chamber are co-cultured with other types of cells in an outer chamber. Here we examined whether the EGF/TGF-alpha-induced tube formation in HOME cells was modulated by human chondrocytes co-culture in the outer chamber. TGF-alpha-dependent tube formation of HOME cells was inhibited when human chondrocytes were co-cultured in the outer chamber. This chondrocyte-induced inhibition of tube formation was partly abrogated by co-administration of anti-TGF-beta antibody. These findings suggest that TGF-beta is partly involved in the human chondrocyte-dependent inhibition of tube formation by human microvascular endothelial cells. This is the first model system demonstrating that avascularity of human chondrocytes is partly due to TGF-beta family produced from them.
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PMID:Inhibition of tubular morphogenesis in human microvascular endothelial cells by co-culture with chondrocytes and involvement of transforming growth factor beta: a model for avascularity in human cartilage. 794 24


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