Molecular mechanisms of fibrin gel clot retraction by platelets and cultured tumor cells.
Using a new quantitative method, we compared the involvement of platelet alpha IIb beta 3 integrin in clot retraction with that in aggregation, and identified a receptor for fibrin gels on the cell surface in the nuclear cell-induced clot retraction. The platelets pretreated with thrombin in the presence of 4 mM EDTA at 37 degrees C completely lost aggregability in response to any agonist, while they were still able to retract clot, though to a less extent than controls. The clot retractions by these pretreated platelets as well as control platelets were inhibited by a monoclonal anti-beta 3 (T74) that also inhibits aggregation. These results suggest that a domain in alpha IIb beta 3 integrin involved in clot retraction is not exactly the same site involved in aggregation (the fibrinogen-binding site). C32TG cells expressing integrin alpha v beta 3 but not alpha IIb beta 3 complex showed an efficient clot retraction, which was inhibited by an anti-alpha v beta 3 antibody but not by Ro-43-5054, a potent inhibitor specific to platelet alpha IIb beta 3. When cDNA of beta 3 was transfected into 293 cells which otherwise lacked beta 3 and a retractile activity, the transfectants retracted significantly fibrin gels, which was specifically inhibited by the anti-beta 3 T74. These findings indicate that alpha v beta 3 is involved in mediating the clot retraction by tumor cells.
Tanoue
K
K
Department of Cardiovascular Research, Tokyo Metropolitan Institute of Medical Science (RINSHOKEN), Japan.
Katagiri
Y
Y
Suzuki
H
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D003018:Clot Retraction; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000097:blood; D009842:Oligopeptides / Q000494:pharmacology; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000911:Antibodies, Monoclonal; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C078174:Ro 43-5054