Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasminogen activator inhibitor-type 1 (PAI-1) was identified in extracts of Lewis lung carcinoma, and its immunohistochemical localization was studied together with that of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators. All primary tumors (n = 11) contained heterogeneously distributed immunoreactivity against each of the three components. Most often, areas that contained u-PA immunoreactivity also contained PAI-1 immunoreactivity. However, several areas showed a strong u-PA immunoreactivity, but no or low PAI-1 immunoreactivity. The latter staining pattern was only found in peripheral areas, and usually in areas with histological signs of tissue destruction. Lung metastases always contained u-PA immunoreactivity, while PAI-1 immunoreactivity was found in most, but not all, metastases. t-PA immunoreactivity was found in a few scattered tumor cells, in primary carcinomas as well as metastases. Controls that included absorption with highly purified antigen preparations and immunoblotting, indicated that all the immunoreactivity represented genuine PAI-1, u-PA and t-PA, respectively. The results are consistent with an assumption that the plasminogen activation system, and particularly u-PA and PAI-1, plays a role in regulation of breakdown of extracellular matrix proteins during invasive growth in this carcinoma.
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PMID:Plasminogen activator inhibitor-type 1 in Lewis lung carcinoma. 210 45

Plasminogen activator is a serine protease which exists in two forms, known as tissue-type plasminogen activator and urokinase-type plasminogen activator. Here, we show that urokinase-type plasminogen activator activity in primary breast carcinomas correlates with both size of tumor and number of axillary nodes with metastases. Patients with primary carcinomas containing high levels of urokinase-type plasminogen activator activity had a significantly shorter disease-free interval than patients with low levels of activity. It is concluded that urokinase-plasminogen activator may be a new prognostic marker in breast cancer.
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PMID:Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report. 313 20

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.
Clin Exp Metastasis
PMID:Secretion of plasminogen activators by human colorectal and gastric tumor explants. 340 59

Fibrinogen degradation products could be detected frequently in patients with metastasized tumour disease. Plasminogen, antithrombin III and fibrinogen were not found to be elevated. The proteinase inhibitors alpha 2-macroglobulin, alpha 1-antitrypsin and C1-esterase inactivator were measured before and after chemotherapy. alpha 1-antitrypsin and C1-esterase inactivator were elevated in patients with pulmonary and/or retroperitoneal metastases. Regardless of the stage of the tumour disease serum level of alpha 1-antitrypsin and C1-esterase inactivator in increased under cytotoxic chemotherapy.
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PMID:[Proteinase inhibitors and fibrinogen split products in patients with malignant diseases (author's transl)]. 616 18

Plasminogen activators are an enzyme complex which first appears in the trophoblast and may contribute to the invasive and metastatic process in neoplastic growth. In this study, 102 cytosols from human breast cancer biopsies were analyzed for PAA (with the chromogenic tripeptide S2251 KABI), steroid receptors (ER and PR), age, nodal and menopausal status. The data were submitted to log (X + 1) transformation and the raw and transformed data were analyzed for distribution. Because of the largely non-normal distribution of the data, Spearman's rank order correlation coefficients were generated to test for relationships between these differentiation markers and the clinical data. Nodal and menstrual status groups were compared for PAA and receptor levels using the Wilcoxon rank sum test. We found significant positive correlations between net PAA and ER (p = 0.0001), net PAA and PR (p = 0.0001), and net PAA and age (p less than 0.05). PAA levels for nodal status groups were found to be significantly different (negative at p less than 0.05). Nodal metastases predict poor prognosis while higher receptor levels indicate a better prognosis. As PAA levels correlate with the above biologic properties of breast tumors, they may provide additional prognostic information, especially in cases in whom auxiliary node status is unknown.
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PMID:Plasminogen activator activity in human breast cancer cytosols. 639 Jun 61

Plasminogen activator activity (PAA) has been detected in various tumor cells or in their excretion products. In some cell systems PAA is a symptom of cell transformation, but its amount is questionably correlated with the invasiveness of the tumor cells. Procoagulant and aggregation activities on platelets, have been demonstrated in various tumor cells. There are weakly correlated with the metastatic potential of these cells. In vivo, the treatment of animals by modifiers of the hemostasis, or of the fibrinolysis systems provides contradictory results. Some reduction of metastatic diffusion and increase of life span have been noted with Warfarin. Clinical trials are scarce and their methodology is debatable. When conclusive, a lengthening of the life span has been observed, but not a reduction of the metastatic spread as metastases were still present.
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PMID:[Hemostasis and tumor invasion. Therapeutic implications]. 639 23

Plasminogen activators (PAs), a family of proteases active in blood coagulation, may play an important role in cancer. Indeed, blood coagulation disorders, such as altered fibrinogen and fibrin metabolism and increased incidence of vascular thrombosis, are common in patients with advanced malignant disease. Different types of human tumors are known to contain high levels of PA. The isoelectric focusing patterns of the PAs present in tumors and plasma from patients with breast cancer were compared with those of purified human urokinase and melanoma tissue PA. The pattern of isoelectric molecular forms of PA active at pH 8 showed two groups of several bands: in plasma from tumor-bearing patients and controls, these groups were in the pl ranges of 6.6 to 6.8 and 8.0 to 8.5; in mammary adenocarcinoma tissue, the ranges were 6.8 to 7.9 and 9.0 to 9.4. These patterns were different from those obtained with purified markers; the latter were 5.8 to 9.4 and 5.9 to 7.6 for purified human urokinase and melanoma plasminogen tissue activator, respectively. PA activity in tumor-bearing patients was very high in malignant tissue and, on the contrary, very decreased in plasma; this latter decrease was correlated with the presence of metastases in the axillary lymph nodes. These results suggest that the high PA activity in the tumor tissue might participate in the destruction of the peritumoral tissue, thus allowing its invasion by tumor cells, whereas the low activity of PA in the plasma might increase plasma fibrin, reflecting thus an early disorder in blood coagulation which would enhance the formation of metastases.
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PMID:Relationship between multiple forms of plasminogen activator in human breast tumors and plasma and the presence of metastases in lymph nodes. 653 66

Cell suspensions from the R 3230 AC rat mammary adenocarcinoma, when injected intravenously into F344 rats, invariably produce multiple lung foci within 10 days. We compared the colonization potential of cultures obtained from these foci and from cell populations exposed to 100 micrograms/ml medium of both concanavalin A and wheat germ agglutinin for 5 passages with the original cell line. Plasminogen activator activity (PAA) was determined in all three cell subpopulations, using S2251 (KABI) as chromogenic substrate. All cell lines retained their ability to grow after subcutaneous implant. The lectin resistant variant was found to have lost its capacity to nidate in the lung completely and also had the lowest PAA. In contrast, the cell population derived from the lung foci ranked highest in PAA.
Invasion Metastasis 1983
PMID:Plasminogen activators as markers of tumor colonization potential. 668 73

Proteolytic activity is important for tumor growth and metastasis. Plasminogen and urokinase-type plasminogen activator (u-PA) constitute one of the most extensively studied proteolytic systems believed to participate in these processes. u-PA cleaves plasminogen to plasmin, which in turn degrades surrounding extracellular matrix and allows tumor cells to migrate to other areas. The specific receptor for u-PA (u-PAR) has also been implicated as an essential modulator in this pathway. Eleven paired samples of colorectal cancers and normal mucosal tissues from the same patients were removed at surgery. The tissues were homogenized and the supernatants assayed for u-PAR immunoreactivity, u-PAR antigen concentration, u-PAR binding activity and u-PA activity. Immunoblot analysis showed that a major u-PAR species of approximately 55 kDa was present in all tissues. In addition, a protein band of approximately 41 kDa, which crossreacted with anti-u-PAR antibodies, was also found in the tumors. This protein band was either absent, or present in relatively small amounts in the normal colorectal tissues. Cross-linking experiments showed that the approximately 55 kDa band only, and not the approximately 41 kDa band, was able to bind either single chain urokinase-type plasminogen activator (scu-PA) or the amino terminal fragment of urokinase (ATF). The tumor samples also exhibited highly elevated u-PA activity and u-PAR antigen relative to the corresponding normal tissues. Elevated u-PA activity appeared to correlate with elevated u-PAR antigen in colorectal cancers, but not in the normal tissues. These increases were also associated with increase of the u-PAR-related, low-molecular-weight protein in the tumor samples. The measurement of u-PAR and the u-PAR-related protein, in addition to u-PA activity, could have diagnostic or prognostic value in this type of cancer.
Clin Exp Metastasis 1995 Nov
PMID:Increase of a urokinase receptor-related low-molecular-weight molecule in colorectal adenocarcinomas. 758 7

Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 micrograms/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 micrograms/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis.
Clin Exp Metastasis 1995 Mar
PMID:Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6. 788 14


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