Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
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Tumor spread may be favored by a reduced production and/or an enhanced degradation of extracellular matrix components (collagen, fibronectin, laminin). Most tumor cell behavior, from growth to spread, may be regulated by cytokines, the exact roles of which, however, are not yet fully understood. We here evaluate the effects of some cytokines (epidermal growth factor, transforming growth factor-beta 1, interleukin-1 alpha, and interleukin-1 beta) on both cell growth and the production of the aminoterminal peptide of type III procollagen, the urokinase plasminogen activator, and the plasminogen activator inhibitor-1 in neoplastic cell lines originating in the pancreas and colon. Cells were stimulated daily with the above cytokines and the aminoterminal peptide of type III procollagen, urokinase plasminogen activator, and plasminogen activator inhibitor-1 were measured in the conditioned media. Epidermal growth factor stimulated cell growth of both cell lines. Transforming growth factor-beta 1 counteracted cell proliferation and stimulated type III procollagen and plasminogen activator inhibitor-1 production only in the colon cancer cell line. Interleukin-1 alpha slightly stimulated cell growth, but inhibited plasminogen activator inhibitor-1 production in both cell lines; interleukin-1 beta did not affect cell growth, but stimulated plasminogen activator inhibitor-1 production by the colon cancer cell line. Our findings suggest that transforming growth factor-beta 1 and interleukin-1 beta may have an antidiffusive effect. These results confirm that cytokine-producing cells have a potential role in stimulating or counteracting tumor growth and spread and also confirm the pivotal role of host-tumor interactions in determining the outcome of a particular neoplasia.
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PMID:Cytokines may influence tumor growth and spread. An in vitro study in two human cancer cell lines. 900 14

Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) system and the family of metalloproteinases (MMPs) catalyse the matrix degradation and remodelling processes characteristic of invasive malignant disorders. In a cohort of 50 patients with chronic myeloproliferative disorders (MPD) serum markers for collagen metabolism were compared to plasma levels of enzymes of the uPA and MMP system. Serum aminoterminal propeptide of type III procollagen (S-PIIINP) (P < 0.0001) concentration was significantly higher in the patients (median 3.7 micro g/L vs. 2.5 micro g/L) compared with controls. In a subgroup analysis comprising patients with myelofibrosis (MF), polycythaemia vera (PV) and essential thrombocythaemia (ET), respectively, S-PIIINP levels differed significantly with the highest values found in patients with MF (MF vs. PV vs. ET; P = 0.0027). Serum concentration of carboxyterminal telopeptide of type I collagen (S-ICTP) (P = 0.0006), reflecting type I collagen degradation, was significantly higher in patients compared with controls (median 4.0 micro g/L vs. 2.7 micro g/L). When comparing S-ICTP measurements between patient subgroups and controls there were only significantly higher values among MF and PV patients (MF vs. controls; P < 0.0001, PV vs. controls; P = 0.0016). A significant correlation between the marker for collagen synthesis (S-PIIINP) and degradation (S-ICTP) (r = 0.59; P < 0.0001) was demonstrated. A correlation analysis between serum markers for bone marrow remodelling processes (S-PIIINP, S-ICTP and S-hyaluronan) and plasma-soluble urokinase plasminogen receptor (suPAR) disclosed a significant relationship between suPAR and S-PIIINP (r = 0.48; P = 0.0009), S-hyaluronan (r = 0.56; P < 0.0001) and S-ICTP (r = 0.47; P = 0.0013), respectively. Plasma levels of MMP-2 and -9 were not correlated to serum markers for collagen metabolism. These findings suggest that enzymes of the uPA system might participate in the bone marrow remodelling processes characteristic of MPD.
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PMID:Collagen metabolism and enzymes of the urokinase plasminogen activator system in chronic myeloproliferative disorders: correlation between plasma-soluble urokinase plasminogen activator receptor and serum markers for collagen metabolism. 1295 Feb 37