Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis was made of plasminogen activator (PA) activities present in 0.125% Triton X-100 extracts of human primary colon carcinomas and of their respective serial subcutaneous xenografts in nude mice. A correlation between tumor invasiveness and PA expression was observed in that primary tumors exhibiting clearly invasive growth patterns demonstrated high concentrations of PAs while subcutaneous xenografts, exhibiting noninvasive pseudobenign growth, contained very low levels of PA activity. The decrease in fibrinolytic activity observed in subcutaneous xenografts was not due to an increase in inhibitors of fibrinolytic activity. Immunologic characterization of PAs in tumor extracts showed that over 90% of human PA activity was of the urokinase type. Furthermore, tumor-derived urokinase was shown to be present in a proenzyme form. It was resistant to diisopropyl fluorophosphate (DFP) and was not inhibited by purified PA inhibitor. However, after its activation into urokinase by plasmin, it was completely inhibited by DFP and PA inhibitor.
 ...
PMID:Human primary colon carcinomas xenografted into nude mice. I. Characterization of plasminogen activators expressed by primary tumors and their xenografts. 309 99

An important step in the transition from adenomatous polyp to invasive carcinoma is the degradation of the epithelial basement membrane. By the generation of plasmin, plasminogen activators may play an important role in regulating the extracellular protease activity required for this event to occur. The production of biofunctional urokinase and of tissue plasminogen activator was therefore investigated in the dimethylhydrazine induced rat model of colorectal neoplasia. Both adenomatous polyps (p values less than 0.001) and colorectal carcinomas (p values less than 0.001) were demonstrated to produce a significant excess of both urokinase and tissue plasminogen activator when compared with macroscopically normal colon. There was, however, no increased production of either enzyme by macroscopically normal preneoplastic colon when compared with control colon. This enhanced capacity of colorectal tumours to produce plasminogen activators and generate plasmin is thus a feature of both the premalignant as well as the malignant phenotype. These enzymes may contribute to the malignant potential of adenomatous polyps and to the invasive capacity of established carcinomas.
 ...
PMID:Plasminogen activators in experimental colorectal neoplasia: a role in the adenoma-carcinoma sequence? 311 68

The human tumor cell line HT-1080 was used as a model system to study the effects of transforming growth factor-beta (TGF beta) on polypeptide synthesis and proteolytic activity of malignant cells. Confluent cultures were exposed to TGF beta under serum-free conditions, and alterations in the production of proteins were examined by metabolic labeling and polypeptide analysis. TGF beta induced the synthesis and secretion of the Mr 47,000 endothelial type plasminogen activator inhibitor (PAI-1) as shown by reverse zymography, immunblotting, and immunoprecipitation analyses. TGF beta-induced PAI-1 was rapidly deposited in the growth substratum of the cells as shown by metabolic labeling and extraction of the cultures with sodium deoxycholate. Using pulse-chase experiments, we found a relatively fast turnover of substratum-associated PAI-1. Exogenously added urokinase released PAI-1 from the substratum even in the presence of the plasmin inhibitor aprotinin, suggesting a direct effect of urokinase. Immunoreactive complexes of higher molecular weight were subsequently detected in the medium. Epidermal growth factor, transforming growth factor-alpha, platelet-derived growth factor, and insulin did not elicit similar effects on the amount of PAI-1. TGF beta also inhibited the anchorage-independent growth of HT-1080 cells at the same concentrations at which it induced PAI-1. These results indicate that TGF beta can modulate the extracellular proteolytic activity of cultured cells by enhancing the secretion and deposition of PAI-1 into their microenvironment. It remains to be established whether TGF beta inhibition of anchorage-independent growth of these cells is associated with the induction of PAI-1.
 ...
PMID:Transforming growth factor-beta induction of type-1 plasminogen activator inhibitor. Pericellular deposition and sensitivity to exogenous urokinase. 312 97

Various human malignant tumors, including malignant melanoma, showed an absence of fibrinolytic activity by the histochemical fibrin slide method. In contrast, a tissue plasminogen activator has been isolated both from extracts of melanoma tissues and melanoma cell lines in culture, and has been characterized to be a potent plasminogen activator. In an attempt to resolve this apparent discrepancy, we studied biopsied specimens of melanoma and several melanoma cell lines by the immunoperoxidase method. Tissue plasminogen activator was observed in melanoma tissues and cell lines while the various inhibitors of fibrinolysis, including alpha 2-anti-plasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, and antithrombin III were found intracellularly only in the melanoma tumor cells, but not in melanoma cell lines. We believe that these inhibitors are derived from the blood and are bound to the tissue plasminogen activator within the melanoma cells. This hypothesis is supported by in vivo studies showing binding of tissue plasminogen activator in cultured cell lines to several inhibitors. Since these are potent inhibitors of fibrinolysis, their presence in tumor cells would explain the lack of fibrinolytic activity in melanoma tissues.
 ...
PMID:Tumor growth and metastases in malignant disease. A review. 314 46

First-trimester normal human trophoblast cells show some phenotypic similarities to malignant cells, e.g., rapid proliferation and ability to invade neighboring tissue, including basement membrane in situ, but do not have the ability for unlimited growth or metastasis. The present study examined whether the invasive ability of normal trophoblast cells is an intrinsic property of these cells, independent of the microenvironment provided by the pregnant uterus, and if so, whether they share some of the molecular mechanisms of invasion exercized by metastatic malignant cells. The ability of in vitro grown human trophoblast lines to invade an epithelium-free human amniotic membrane was measured from the temporal kinetics of retention of radioactivity within this membrane resulting from a penetration by 125I-iododeoxyuridine-labeled trophoblast cells. The magnitude of this invasion was compared to that of the highly metastatic human JAR-choriocarcinoma cell line and murine B16F10 melanoma line. Trophoblasts were found to share some of the same molecular mechanisms of invasion with the metastatic cell lines. Inhibitors of collagenase, plasmin, plasminogen, and plasminogen activators completely prevented invasion of the amnion by the trophoblast lines as well as by the metastatic JAR and B16F10 lines. Mersalyl, a compound known to activate collagenase, stimulated invasion by all cell lines tested, including under conditions in which plasmin activity was inhibited. In addition, trophoblasts produced significant levels of type IV collagenase and laminin, both of which appear to be important products of metastatic tumor cells required for basement membrane invasion. It may be concluded from these findings that the invasive property of first trimester human trophoblasts is genetically determined; that the magnitude of amnion invasion cannot differentiate between metastatic cell lines and invasive but nonmetastatic cell lines; and that invasiveness is not a sufficient prerequisite for metastatic ability.
 ...
PMID:Normal nonmetastatic human trophoblast cells share in vitro invasive properties of malignant cells. 317 Jun 42

The proteolytic activities of human tumor cell lines deriving from bronchial squamous cell carcinoma, a lung metastasis of an embryonal rhabdomyosarcoma and a pleural mesothelioma were measured by use of chromogenic substrates. N-acetyl-alanine aminopeptidase activity, plasminogen activator activity, H-D-Ile-Pro-Arg-p-NA splitting activity as well as plasmin-like activity, cathepsin G-like activity and plasma-kallikrein-like activity were found in cell lysates. The enzymatic activity of N-acetyl-alanine aminopeptidase, plasminogen activator and H-D-Ile-Pro-Arg-p-NA splitting activity changed during culturing. Plasminogen activator and H-D-Ile-Pro-Arg-p-NA splitting activity decreased to very low values, whereas N-acetyl-alanine aminopeptidase activity leveled at 1 x 10(-5) mU/cell. Unlike other proteolytic activities, plasminogen activator was released into the medium. Plasminogen activator activity could be measured in culture medium which contained no fetal calf serum.
 ...
PMID:Proteolytic activity of human tumor cell lines deriving from bronchial squamous cell carcinoma, pulmonary metastasis of rhabdomyosarcoma and pleural metastasis of mesothelioma. 332 2

The ability of B16-F10 mouse melanoma cells to cross an amnion basement membrane was determined in the presence of strong inhibitors of both serine and cysteine proteases. The concentrations of inhibitors were at orders of magnitude higher than their Ki values to serine and cysteine proteases implicated in metastasis, thus ensuring a complete inhibition for tumor secreted proteases such as cathepsin B-like proteases, plasminogen activators, and plasmin. Under these conditions of high serine and cysteine protease inhibitor concentrations, no significant decrease in B16-F10 melanoma cell invasion through the amnion was observed. Separate experiments showed that the inhibitors were neither toxic to the cells nor degraded. The results show that neither tumor cell secreted cathepsin B-like proteases nor plasminogen activator have a controlling role in basement membrane crossing in this metastatic model. A possible role for tumor cell membrane proteases in basement membrane invasion, in which the substrates of the protease bind to receptor sites near a membrane associated proteolytic activity, is not eliminated.
 ...
PMID:Inhibition of proteolytic enzymes in the in vitro amnion model for basement membrane invasion. 352 1

Elevated levels of plasminogen activator (PA) activity have been correlated with neoplasia and may have an important role in tumor-cell invasion and metastasis. We have developed a new caseinolytic assay that uses an immunochemical approach to measure the activity of PA elaborated by malignant tumor cells. The highly sensitive assay consists in incubating a source of PA (viable tumor cells, cell extracts, or conditioned medium) with purified plasminogen in microtiter plates precoated with a suitable protein substrate such as casein. Clearance of the immobilized protein substrate by PA-generated plasmin is then measured by a technique based on the enzyme-linked immunosorbent assay. In experiments using urokinase as a source of PA, the assay displayed near linearity over several log units of urokinase activity and could detect as little as 10(-2) Ploug units of PA activity. Besides successfully measuring PA activity produced by the human HT 1080 fibrosarcoma cell line, the assay permitted detection of significant plasminogen-independent proteolytic activity generated by intact tumor cells cultured in direct contact with immobilized protein substrates.
 ...
PMID:Measurement of plasminogen activator activity from human fibrosarcoma cells by a new microassay. 369 27

Hypofibrinogenemia and disseminated intravascular coagulation are common events in patients with metastatic prostate carcinoma. This study tests the hypothesis that prostate tumor growth and metastasis is associated with sustained activation of fibrinolysis secondary to increased release of plasminogen activator. We implanted an androgen-insensitive prostate tumor into an inbred strain of rats and serially measured plasminogen, plasminogen activator, plasmin and fibrinogen. Control groups included animals without tumor and a group implanted with transitional cell bladder carcinoma, a locally infiltrating tumor not usually associated with hemostatic complications. Our results showed a significant and steady rise in plasma plasminogen activator, plasmin and fibrinogen levels in animals implanted with prostate cancer. This, however, is not specific for prostate tumor. Similar, perhaps more profound changes were noted in animals implanted with the transitional cell carcinoma.
 ...
PMID:The fibrinolytic system in experimental prostate tumor. 381 May 52

Bovine aortic endothelial cells (BAEC) were grown on extracellular matrices produced by vascular smooth muscle cells or fetal bovine endothelial cells. The glycoprotein components of these complex substrates were degraded through activation of the serum zymogen plasminogen to plasmin, as well as by a plasminogen independent protease(s). The plasminogen independent enzyme might be a protease with elastolytic activity since the BAEC digested elastin present in smooth muscle cell derived matrices. The cells also displayed collagenolytic activity on both types of matrices. The addition of the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) (10(-7) M) to the culture medium enhanced considerably the plasminogen activator and collagenolytic activities elaborated by BAEC resulting in an increased degradation rate of matrix glycoprotein and collagen components, whereas the elastolytic activity remained unaffected. Dexamethasone (10(-7) M), although suppressing plasminogen activator (PA) production by BAEC, did not alter their elastolytic activity allowing the cells to degrade the glycoprotein components of the matrices at an unchanged rate. The collagenolytic activity of the BAEC remained unaffected by dexamethasone. These studies demonstrate that BAEC elaborate different proteolytic enzyme activities allowing them to degrade various components of extracellular matrices. These enzymatic activities may be modulated by certain agents thus changing the degradative capabilities of the BAEC.
 ...
PMID:Endothelial cells degrade extracellular matrix proteins produced in vitro. 408 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>