Inhibition of mammary tumor cell adhesion, migration, and invasion by the selective synthetic urokinase inhibitor B428.
We have analyzed the anti-invasive properties of the selective synthetic urokinase inhibitor 4-iodo benzo[b]thiopene-2-carboxamidine (B428) in the mouse mammary carcinoma model F3II. At non-cytotoxic concentrations (10-20 microM), B428 blocked secreted and cell-associated tumor-derived urokinase activity as well as whole cell plasminogen-dependent casein degradation. Pretreatment of F3II monolayers with B428 enhanced membrane bound uPA, suggesting that the compound may modify urokinase receptor mobilization and urokinase-dependent cell signaling. B428 exerted a dose-dependent inhibition of Matrigel invasion by F3II cells and also reduced tumor cell adhesion and migration using the same doses. Our data indicate that uPA and its cell surface receptor are involved in attachment, migration, and invasion of mammary tumor cells, and that the three processes can be blocked by a synthetic urokinase inhibitor.
Alonso
D F
DF
Department of Science and Technology, Quilmes National University, Buenos Aires, Argentina. dfalonso@unq.edu.ar
Tejera
A M
AM
Farias
E F
EF
Bal de Kier Joffe
E
E
Gomez
D E
DE
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D013876:Thiophenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
C097398:4-iodine-benzo(b)thiophene-2-carboxamidine; D000578:Amidines; D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D005353:Fibronectins; D013876:Thiophenes; D014568:Urokinase-Type Plasminogen Activator