uPA and uPAR contribute to NK cell invasion through the extracellular matrix.
BACKGROUND
The urokinase plasminogen activator (uPA) system has been implicated in cellular invasiveness of tumor cells and immune cells. Herein we provide evidence for the production by natural killer (NK) cells of both uPA and its receptor (uPAR).


METHODS
Western blot analysis, RTPCR, casein/plasminogen zymography, and fluorescence microscopy were employed to detect uPA and uPAR on NK cells. NK cell invasiveness was examined using Matrigel invasion assays.


RESULTS
NK cell uPA appeared at its characteristic molecular weights, is enzymatically active in casein/plasminogen zymography, and is recognized by monoclonal antibodies. uPAR was detected by RTPCR and fluorescence microscopy. Matrigel invasion assays demonstrated an active role of uPA in NK cell invasion.


CONCLUSIONS
The uPA system contributes to extracellular matrix (ECM) degradation by NK cells, which may be essential for NK cell accumulation into metastases, and may be prerequisite for their killing of tumor cells following NK cell adoptive transfer.
Al-Atrash
G
G
Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth 76107-2699, USA.
Kitson
R P
RP
Xue
Y
Y
Mazar
A P
AP
Kim
M H
MH
Goldfarb
R H
RH
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D007611:Aprotinin / Q000378:metabolism; D015153:Blotting, Western; D002364:Caseins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D010641:Phenotype; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010958:Plasminogen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010738:Type C Phospholipases / Q000494:pharmacology; D020298:U937 Cells; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D002364:Caseins; D004338:Drug Combinations; D007797:Laminin; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011509:Proteoglycans; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C059485:matrigel; D010958:Plasminogen; D003094:Collagen; D007611:Aprotinin; D010738:Type C Phospholipases; D014568:Urokinase-Type Plasminogen Activator; D043265:Phosphatidylinositol Diacylglycerol-Lyase