uPA and uPAR contribute to NK cell invasion through the extracellular matrix

Background: The urokinase plasminogen activator (uPA) system has been impli cated in cellular invasiveness of tumor cells and immune cells. Herein we p rovide evidence for the production by natural killer (NK) cells of both uPA and its receptor (uPAR). Materials and Methods: Western blot analysis, RTP CR, casein/plasminogen zymography, and fluorescence microscopy were employe d to detect uPA and uPAR on NK cells. NK cell invasiveness was examined usi ng Matrigel invasion assays. Results: NK cell uPA appeared at its character istic molecular weights, is enzymatically active in casein/plasminogen zymo graphy, and is recognized by monoclonal antibodies. uPAR was detected by RT PCR and fluorescence microscopy. Matrigel invasion assays demonstrated an a ctive role of uPA in NK cell invasion. Conclusion: The uPA system contribut es to extracellular matrix (ECM) degradation by NK cells, which may be esse ntial for NK cell accumulation into metastases, and may be prerequisite for their killing of tumor cells following NK cell adoptive transfer.