Secreted and membrane-associated matrix metalloproteinases of IL-2-activated NK cells and their inhibitors

We have previously documented that rat IL-2-activated NK (A-Ng) cells produ ce matrix metalloproteinase-2 (MMP-2) and MMP-9, In this study, we describe mouse A-NK cell-derived MMPs, including MT-MMPs, and also TIMPs. RT-PCR an alysis from cDNA of mouse A-NK cells revealed mRNA for MMP-2, MMP-9, MMP-11 , MMP-13, MT1-MMP, MT2-MMP, TIMP-1, and TIMP-2, MMP-2 and MMP-9 expression was confirmed by gelatin zymography, Moreover, we report for the first time that MT-MMPs are expressed by NK cells, i.e., large granular lymphocytes a s determined by both RT-PCR and Western blots. TIMP-1 expression was detect ed as a 29-kDa protein in Western blots. It is intriguing that TIMP-2 prote in from A-NK cells was also detected as a 29-kDa protein, which is clearly different from the previously reported molecular mass of 21 kDa in mouse an d human cells. In addition, inhibition of MMPs by BB-94, a selective inhibi tor of MMP, significantly inhibited the ability of mouse A-NK cells to migr ate through Matrigel, a model basement membrane. Taken together, these find ings suggest that A-NK cells may therefore use multiple MMPs in various cel lular functions, including degradation of various extracellular matrix mole cules as they extravasate from blood vessels and accumulate within cancer m etastases following their adoptive transfer.