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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extravascular coagulation and fibrinolysis are intimately involved in and modulate cancer cell growth, invasion and metastasis. Samples from resection specimens of patients with primary lung cancer (adenocarcinomas) were tested with monoclonal (MAb) and polyclonal (PAb) antibodies against various factors of the coagulation or fibrinolysis systems, or against antigens of inflammatory or proliferating cells. MAb Ki-67 specific to nuclear antigens of proliferating cells showed a distinct but variable staining of cell nuclei throughout the tumor tissue. Nests of tumor tissue stained with cytokeratin-specific antibodies (PKK1), whereas other parts were negative. Fibrin(ogen) and fibronectin were found throughout the tumor tissue stroma and in the alveolar lining, and the most densely stained areas were at the transition zone between normal and tumor tissue. Fibrinolytic system components like tissue plasminogen activators (t-PA), and urokinase (u-PA), and their inhibitors PAI-1 and PAI-2 were all studied. All specimens were negative for t-PA (except endothelial linings), whereas urokinase-specific antibodies stained loosely packed tumor cells and macrophages within the tumor stromal tissue and alveolar septa. Both PAI-1 and PAI-2 were most prominently expressed within interstitial and alveolar macrophages. A weaker staining of tumor tissue cells was demonstrated. Inflammatory cells like macrophages and T lymphocytes were located in aggregates or diffusely spread within tumor stromal tissue. The inflammatory reaction was most intense at the border between normal lung and tumor tissue.
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PMID:Immunohistochemical localization of coagulation, fibrinolytic and antifibrinolytic markers in adenocarcinoma of the lung. 172 Mar 19

In an earlier publication (Harvey, et al. (1982) J. Biol. Chem., 257, 5645-5651) the discovery of a family of unusually large molecules with plasminogen activator activity in the conditioned medium of a human lung cancer cell line was reported. These molecules are related to urokinase (uPA) by functional and immunological criteria. We have now purified two representatives of this glycoprotein family of Mr 900,000 (PA900) and Mr 660,000 (PA660). While these could be fractionated into subspecies exhibiting size and charge differences, reduction yielded in all cases two predominant chains of 70 and 40 kDa, respectively. Since the amino acid composition of the subfractions was identical, we conclude that the heterogeneity is due to demonstrated differences in glycosylation. The amino acid composition of the unreduced species and of the major reduced chains differed from that of 55 kDa uPA. These enzymes are active toward the substrate, plasminogen, as well as toward the uPA-specific synthetic substrate, Spectrozyme UK, and these activities are inhibitable by diisopropylphosphorofluoridate (DFP). Treatment of PA660 with [3H]DFP resulted in the incorporation of 1.4 mol of DFP into 1 mol of enzyme, suggesting the presence of a single active site. The label was quantitatively recovered in a 21 kDa fragment in a reduction experiment. This fragment also demonstrated immunological reactivity with antiurokinase. It is postulated that PA660 is composed of five or six pairs of the 70 and 40 kDa chains, and of a single uPA-like entity. All of these chains are linked by disfulfide bonds. Whether larger portions of uPA are also present in this molecule, is not yet clear. By electron microscopy, PA900 shows a filamentous structure, while PA660 is predominantly globular. The occurrence of large uPA-like activators in extracts of human colon carcinomas that crossreact with monospecific antibody against uPA, is discussed.
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PMID:Characterization of a family of high-molecular-weight plasminogen activators secreted by a lung tumor cell line. 185 26

A new cell line (LC-1/sq) of human lung squamous-cell carcinoma was established from a surgically resected specimen of primary lung cancer. Upon continuous propagation in serum-free culture medium, it secreted trypsin inhibitors into the conditioned medium. The major fraction of the trypsin inhibitor (T1-1) was purified to apparent homogeneity by anion-exchange and gel-filtration high-performance liquid chromatography (HPLC) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by transblotting to Immobilon. T1-1 effectively inhibited trypsin. Chymotrypsin, plasmin and kallikrein were inhibited to a lesser extent, but urokinase-type plasminogen activator, elastase, thrombin and papain were not inhibited. The activity of T1-1 was acid-stable and heat-resistant, and its molecular weight was 115 kDa by SDS-PAGE. It exhibited single NH2-terminal sequence, and its first 20 NH2-terminal amino-acid residues were identical with those of protease nexin-II (PN-II)/amyloid beta-protein precursor (APP). These characteristics of T1-1 suggest that the major trypsin inhibitor secreted by LC-1/sq is indistinguishable from PN-II/APP. LC-1/sq is the first lung squamous carcinoma cell line that secretes functionally active trypsin inhibitor, PN-II/APP, in vitro and is useful for studying its biological significance in malignant tumor.
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PMID:Establishment of a new human cancer cell line secreting protease nexin-II/amyloid beta protein precursor derived from squamous-cell carcinoma of lung. 191 42

The potential importance of pleural fibrin deposition in the pathogenesis of pleural injury is supported by both clinical and experimental observations. We hypothesized that the local equilibrium between procoagulant and fibrinolytic activities is disrupted to favor fibrin deposition in exudative pleuritis. To test this hypothesis, we characterized procoagulant and fibrinolytic activities in pleural exudates from patients with pneumonia, lung cancer, or empyema and transudates from patients with congestive heart failure. Procoagulant activity was generally increased in exudative processes and was due mainly to tissue factor. All effusions contained antithrombin III and inhibited factor Xa and thrombin, but endogenous prothrombinase or thrombin activities were variably detected. Pleural fluid fibrinolytic activity was increased in congestive heart failure and was due to both tissue plasminogen activator and urokinase. Depressed fibrinolytic activity was found in pleural exudates despite increased concentrations of plasminogen, mainly glu-1-plasminogen, and was due to inhibition of plasminogen activation by plasminogen activator inhibitors 1 and 2 and of plasmin, in part by alpha 2-antiplasmin. Concentrations of PAI-1 in exudative pleural fluids were increased up to 913-fold, compared with normal pooled plasma. Exudative pleural effusions are characterized by increased procoagulant and depressed fibrinolytic activity, favoring fibrin deposition in the pleural space. The balance of these activities is reversed and favors fibrin clearance in congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormalities of pathways of fibrin turnover in the human pleural space. 206 28

Cell membranes from ten non-small cell lung cancers and four specimens of adjacent lung tissue were assessed for the presence of urokinase type plasminogen activator (uPA) receptors. Displacement binding studies using 125I labelled urokinase showed specific binding on lung cancer and lung membrane preparations. Scatchard analysis showed that the dissociation constant of high affinity sites on tumour membranes was 2.9 x 10(-11) M/1 and on lung membranes was 2 x 10(-9) M/1. The concentration of high affinity binding sites on tumour membrane was 54 fmol/mg of membrane protein and on normal lung membrane was 170 fmol/mg protein. Two-point binding assays showed specific binding of urokinase on five of eight tumour membranes and one of three normal lung membranes. There was no correlation between the amount of urokinase bound and tumour subtype or extent of disease. Because of interactions between uPA and epidermal growth factor receptors (EGFr) in cell culture and because lung cancers express increased EGFr we studied the association of uPA receptors and EGFr. Seven tumours expressed EGFr at 6.8-67.6 fmol/mg of protein of EGFr and four normal lung membranes had EGFr at 5.2-15.6 fmol/mg protein EGFr. There was no correlation between uPA receptors and EGFr in this series. We conclude that non-small cell lung cancers carry receptors for urokinase and this provides a novel mechanism for control of local proteolysis.
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PMID:Urokinase receptors in lung cancer and normal lung. 216 Nov 99

Human non-small lung cancer cell lines HS-24 (established from a primary squamous cell carcinoma) and SB-3 (established from a metastasis of a primary adenocarcinoma of the lung into the adrenal gland) were analysed for the proteinases tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator inhibitor (PAI-1). The proteinases were characterized by activity measurements, inhibition studies, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. Cell-associated proteinases were determined in cell lysates, secreted proteinases in cell conditioned culture media. Both cell lines were found to secrete uPA and PAI-1, whereas tPA could be detected only in HS-24 conditioned media. No cathepsin B activity could be detected in media of both cell lines. However, activation experiments and western blot analysis showed, that at least HS-24 secrete an inactive precursor. Cell lysates of HS-24 and SB-3 show PA activity, but on a low level. Cathepsin B activity was also found to be low in HS-24 lysates. However, SB-3 lysates show high cathepsin B activity. Further characterization of the proteinases by their sensitivity against several inhibitors suggests that they are similar to the corresponding proteinases of normal, nonmalignant cells.
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PMID:Detection of cathepsin B, plasminogen activators and plasminogen activator inhibitor in human non-small lung cancer cell lines. 222 60

Conditioned media from explants of human colorectal and gastric tumors in short-term organ culture were analysed for plasminogen activator activity, activity toward the synthetic urokinase substrate, Spectrozyme-UK, and for the presence of urokinase antigen using monospecific goat antibody, by enzyme-linked immunosorbent assay. Comparisons were made between primary tumors, adjacent normal mucosa and metastatic lesions. These analyses were carried out on unfractionated culture fluids and on fractions obtained by fast protein liquid chromatography separation using Superose 6 gels. Plasminogen activator activity, tested by azocaseinolysis in the presence of added plasminogen, was restricted to peaks of 55 kD and 155 kD. These were of the urokinase type as shown by specific immunoinhibition and by absorption by an antiurokinase antibody-Affigel 10 column. Spectrozyme-UK, in addition to these peaks, detected a series of higher molecular weight activities, the largest of which appeared in the void volume, and were therefore of greater than 10(6) molecular weight. These activities were greatly increased by inclusion of trace plasmin indicating that these components were mostly in their proenzyme forms. The characteristics of these very large enzymes were similar to those isolated earlier from a human lung cancer cell line. Comparison of the primary and metastatic tumors confirmed earlier observations showing that urokinase secretion by the metastatic tumors was greatly reduced in comparison with the primary tumors: in the colon carcinomas it was 10 per cent of the value for the primary, in the gastric tumors 3 per cent, whether means or medians were compared (P less than 0.0001). This large difference was characteristic only of plasminogen activator secretion assayable by azocaseinolysis; activities toward Spectrozyme-UK, and antigen reacting with anti-urokinase antibody, were considerably less different in the two groups. In individual tissues, no correlation was found between the amount of extractable plasminogen activator and amounts secreted, or between the latter and the amount of lactic acid released. It is postulated that the greatly reduced plasminogen activator secretion by explants of metastatic tumors may be a phenotypic characteristic of distinct advantage for cancer cells destined to initiate metastatic foci, and may contribute to the ability of circulating cancer cells to lodge in the blood vessels of the target organ.
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PMID:Secretion of plasminogen activators by human colorectal and gastric tumor explants. 340 59

Fibrinolysis-inhibitory activity was estimated in the lysates of 21 lines of cultured human cancer cells, from which plasminogen activator activity had veen effectively eliminated by affinity chromatography. Inhibitory activity against urokinase varied from one line to another. Three lines of lung cancer and 1 line of urinary bladder cancer showed high inhibitory activity against urokinase. Two lines of lung cancer, 3 lines of gastric cancer, 1 line of renal cancer and 1 line of renal pelvic cancer showed moderate inhibitory activity. Since inhibitory activity against plasmin was not apparent in all the cell lines tested, this activity seemed to be directed selectively towards urokinase. No inhibitory activity against urokinase was detected in 4 lines of lung cancer, 5 lines of gastric cancer and 1 line of renal cancer. There was no specific correlation between the degree of inhibitory activity against urokinase and the histological cell types of the original tumors of the cultured cell lines.
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PMID:Fibrinolysis-inhibitory activity of cultured human cancer cell lines. 645 67

Immunological similarities or differences between urokinase and plasminogen activators from 9 lines of cultured human cancer cells with varying degrees of fibrinolytic activity were examined with antibodies against human urokinase. The antibodies completely inhibited the fibrinolytic activity of 4 lines of gastric cancer, 2 lines of lung cancer, 1 line of urinary bladder cancer and 1 line of renal cancer, indicating that the plasminogen activators from these cell lines were immunologically identical to urokinase. In 5 out of these cell lines, immunological identity was also confirmed by double diffusion analysis. The plasminogen activator from 1 line of lung cancer was found to be immunologically dissimilar to urokinase by a neutralization experiment and double diffusion analysis. These findings indicate that there are at least two immunologically distinguishable forms of plasminogen activators from human cancer cells.
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PMID:Immunological analysis of plasminogen activators from cultured human cancer cells. 677 12

The HPL-SK-1 cell line derived from the pleural exudate of a lung cancer patient has been shown to secrete plasminogen activators of very high molecular weights (greater than or equal to 2 and 1 million), as shown by gel filtration on Sepharose 6B or CL-6B. The size of these activators could not be reduced by chromatography in buffers containing 2% sodium dodecyl sulfate, 8 M urea, or 1 M KSCN. Goat anti-urokinase antibody inhibited these activators only partially. Trypsin digestion of the 2 million-dalton species yielded several active fragments including one of the size of urokinase, 55,000 daltons. These large activators could be purified only by a double antibody immunoadsorption technique which consisted of the formation of a soluble immune complex between the activators and goat anti-urokinase IgG, followed by the adsorption of this complex to rabbit anti-goat IgG coupled to Affi-Gel 10. The eluted activators were purified 50-fold (2 million daltons) and 130-fold (1 million daltons), respectively. Reduction of the two largest species in the presence of sodium dodecyl sulfate resulted in the appearance of smaller molecular weight active fragments of differing size, indicating that these activators are disulfide-linked oligomers. Among the fragments of the 2 million-dalton species was found a 10,000-dalton enzyme which had lost activator and antigenic specificity and retained only a non-specific protease activity. A similar fragment was also isolated from reduced, purified 55,000-dalton urinary urokinase.
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PMID:Urokinase-like plasminogen activators of unusually high molecular weight secreted by a cell line derived from a human lung cancer case. 704 Mar 69


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