Cooperation of urokinase plasminogen activator and matrix metalloproteinases in NK cell invasion.
We have previously investigated the role of the urokinase plasminogen activator (uPA) system in NK cell invasion. We have also studied NK cell-derived matrix metalloproteinases (MMPs) in extracellular matrix (ECM) degradation. We now report that both enzyme systems cooperate in NK cell invasion. Zymographic analyses detected uPA in RNK-16 cell conditioned media (CM) with the same molecular weights as the uPA we have previously shown to be associated with the rat NK cell urokinase plasminogen activator receptor. The combination of aprotinin, an inhibitor of plasmin, and Batimastat (BB94), an inhibitor of MMPs, in Matrigel invasion assays showed a more potent inhibitory effect on NK cell invasion than either inhibitor alone. Finally, a down regulation of uPA mRNA was noted following RNK-16 stimulation with collagen IV, fibronectin, and laminin.
al-Atrash
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G
Department of Molecular Biology and Immunology, and Institute for Cancer Research, University of North Texas Health Science Center at Fort Worth Texas, USA.
Kitson
R P
RP
Xue
Y
Y
Goldfarb
R H
RH
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000737:chemistry; D015536:Down-Regulation; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000201:enzymology*; D007797:Laminin / Q000494:pharmacology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013876:Thiophenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D017077:Culture Media, Conditioned; D005353:Fibronectins; D007797:Laminin; D012333:RNA, Messenger; D013876:Thiophenes; D010649:Phenylalanine; D003094:Collagen; D007611:Aprotinin; C080985:batimastat; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases