Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report identifies a component of normal human fibroblasts that forms a covalent linkage with thrombin and urokinase (urinary plasmingoen activator) and mediates most of the specific cellular binding of these proteases. This component, here named protease-nexin (PN), is both associated with the cell surface and released into the culture medium. In several ways PN resembles antithrombin III (AT3), a prominent inhibitor of thrombin in serum: PN links thrombin, probably via an ester bond; PN does not link thrombin blocked at its catalytic site serine; PN has a high-affinity heparin-binding site; and heparin greatly accelerates the rate of linkage between soluble PN and thrombin. Despite these similarities, PN and AT3 are distinct; they differ in size and are not immunologically cross-reactive. Whereas AT3 regulates the proteolytic activity of thrombin in serum, PN may regulates the activity of serine proteases at and near the cell surface.
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PMID:Protease-nexin: a cellular component that links thrombin and plasminogen activator and mediates their binding to cells. 615 79

Metastasis represents a hallmark of the tumor cell's escape from normal cellular behavior to acquired invasive and migratory style. Metastasis of prostate cancer (Pca) depends upon the interplay of a series of hematogenous and hematopoietic factors. We investigated the role of some of those factors implicated in the dissemination process in two separate sublines of adenocarcinoma of the prostate. Our data revealed that (1) the urokinase plasminogen activator activity was significantly higher in R3327-AT3, an aggressive metastatic tumor, as compared to R3327-G, a nonmetastatic tumor of the prostate, (2) the concentration of platelets decreased, and the platelet-aggregating activity increased significantly when the platelets were reacted with exogenous aggregating agents and tumor effusions to suggest that activation of the hemostatic system could protect tumor cells from immunosurveillance and facilitate the process of hematogenous dissemination, and (3) transferrin, which has been reported to have a growth-promoting effect on Pca, did not show any appreciable effect on tumor growth but did alter the level of in vitro adherence which possibly could lead to better attachment and increased invasive behavior of tumor cells.
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PMID:Metastatic behavior of prostatic tumor as influenced by the hematopoietic and hematogenous factors. 898 19

The diuretic drug amiloride (AMLD), which competitively inhibits the catalytic activity of urokinase plasminogen activators (UPA), was used to study its effects on the proteolytic enzymes implicated in the invasiveness and metastases in a prostatic tumor model carrying two different sublines of adenocarcinoma of the prostate. Our data showed that UPA activity was significantly higher, both in the cytosol and pellet of R3327-AT3, a fast-growing highly metastatic and androgen-insensitive tumor, as compared to the G3327-G subline, a slow-growing nonmetastatic tumor of the prostate. The UPA activity in AT3 tumor dropped when the rats were treated with AMLD for 3 weeks. The UPA activity in the sera and tumor effusions from rats with AT3 tumor was significantly higher as compared to those with G subline tumor. The number of pulmonary metastatic foci was the same in untreated rats as compared to those treated with AMLD. The lymph node inspection after 3 weeks revealed no secondary tumor in the AMLD-treated group. The role of UPA in the metastases of prostate cancer is discussed.
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PMID:Inhibitory effect of amiloride on the urokinase plasminogen activators in prostatic cancer. 942 83