Balb/c 3T3 cultures grown in the absence of serum release both plasminogen activator and plasminogen activator inhibitor in the culture medium. Cellular transformation with SV-40 virus increased the level of the activator, whereas dexamethasone increased the level of the inhibitor. Heparin added to the medium potentiated the glucocorticoid-induced inhibitory activity, strongly decreasing or completely abolishing the activity of plasminogen activator. Heparin sulfate showed similar effects to heparin, although at higher concentrations. It is suggested that heparin-like compounds are involved in the regulation of plasminogen activator, acting as inhibitory cofactors.
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References
1.
ChiarugiV.P.: Glycosaminoglycans and neoplastic transformation.Anticancer Res., 2: 275–282, 1982.
2.
ChiarugiV.P., VannucchiS.: Surface heparan sulphate as a control element in eukariotic cell.J. Theor. Biol., 12: 459–469, 1976.
3.
ChiarugiV.P., Del RossoM., VannucchiS., FibbiG., PasqualiF.: Studies on heparin dependent protease inhibitors.Extracellular Matrix (HawkesS. & WangJ. L. Eds.), pp. 353–363, Academic Press, London and New York, 1982.
4.
ColemanP.L., BarouskiP.A., GelertherT.D.: The dexamethasone induced inhibitor of fibrinolytic activity in hepatoma cell.J. Biol. Chem., 257: 4260–4267, 1982.
5.
CrutchleyD.J., ConanL., MaynardJ.R.: Human fibroblasts produce inhibitor directed against plasminogen activator when treated by glucocorticoids.Ann. New York Acad. Sci., 370: 600–616, 1981.
6.
DanielssonA., BjörgI.: Decreased binding of heparin to antithrombin follows the interaction between antithrombin and thrombin.Biochem. J., 207: 21–28, 1982.
7.
FolkmanJ.: Angiogenesis inhibition and tumour regression caused by heparin or heparin fragments in the presence of cortisone.Science, 221: 719–724, 1983.
8.
HolmbergL., BladtB., AstetdB.: An inhibitor from human placenta specifically binds urokinase and inhibits plasminogen activator released from ovarian carcinoma in tissue culture.Biochim. Biophys. Acta, 445: 215–222, 1976.
9.
HolzerH., HeinrichP.C.: Control of proteolysis.Ann. Rev. Biochem., 49: 63–91, 1980.
10.
LaemliU.K.: Cleavage of structural proteins during assembly of the head of bacteriophage T 4.Nature, 227: 680–685, 1970.
11.
LowD.A., BakerJ.D., KoonceW.C., CunninghamD.D.: Released protease nexin regulates cellular binding, internalization and degradation of serine proteases.Proc. Natl. Acad. Sci. U.S., 78: 2340–2344, 1981.
12.
LoskutoffD.J., EdgigtonT.S.: Synthesis of fibrinolytic activator and inhibitor by endothelial cells.J. Biol. Chem., 256: 4142–4154, 1981.
QuigleyJ.P.: Phorbol ester-induced morphological changes in transformed chick fibroblasts: evidence for direct catalytic involvement of plasminogen activator.Cell, 17: 131–132, 1979.
15.
RifkinD.B.: An enzymatic function associated with transformation of fibroblasts by oncogenic viruses.J. Cell. Physiol., 97: 379–384, 1978.
16.
ReichE.: Proteinases and tumour invasion.Biological Markers of Neoplasia (RuddonR.W. Ed.), pp. 491, Elsevier, North Holland, 1978.
17.
RoblinR.: Plasminogen activator and cellular transformation.Biological Markers of Neoplasia (RuddonR.W. Ed.), pp. 241, Elsevier, North Holland, 1978.
18.
WeinsteinB., WiglerM., YamasakiH., LeeL., FisherP.B., MufsonA.: Regulation of the expression of certain biological markers of neoplasia.Biological Markers of Neoplasia (RuddonR.W. Ed.), pp. 541, Elsevier, North Holland, 1978.
