The expression and localization of urokinase-type plasminogen activator and its type 1 inhibitor are regulated by retinoic acid and fibroblast growth factor in human teratocarcinoma cells.
Human Tera 2 embryonal carcinoma cells switch gradually from rapidly growing undifferentiated cells to almost nonproliferating cells during retinoic acid (RA)-induced neuronal differentiation. This process is associated with the increased expression of type 1 plasminogen activator inhibitor (PAI 1) mRNA, and the secreted inhibitor is immobilized to the pericellular area. Furthermore, the differentiation is accompanied by a decrease in the amount of both the secreted tissue-type PA (tPA) and the mainly cell-associated urokinase-type PA (uPA) activity. In RA-differentiated cells, uPA becomes localized at the vinculin-rich cell-substratum adhesion sites. Fibroblast growth factor activity has been associated with various events during embryonal growth and with the regulation of proteolytic enzymes. A short-term treatment of the undifferentiated Tera 2 cells with basic fibroblast growth factor (bFGF) increases uPA mRNA levels and the cell-associated uPA activity, whereas the secretory tPA activity decreases. bFGF induces PAI 1 mRNA expression in the undifferentiated cells, but unlike PAI 1 protein after RA-treatment, the inhibitor does not accumulate around the cells but is released in the medium. A similar exposure to bFGF has less effect on the RA-differentiated Tera 2 cells. Under these conditions bFGF treatment leads to an increase in the amounts of PAI 1 and uPA mRNAs, but no changes in the localization of these components can be seen. Differentiation of human embryonal carcinoma cells is thus connected with an altered response to bFGF.
Tienari
J
J
Department of Pathology, University of Helsinki, Finland.
Alanko
T
T
Lehtonen
E
E
Saksela
O
O
D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005342:Fibrinolysis; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013724:Teratoma; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016596:Vinculin
D003598:Cytoskeletal Proteins; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D016596:Vinculin; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator