Abstract
NK (Natural killer) cells have the ability to migrate and eliminate tumor cells. We evaluated the role of matrix metalloproteinases-1 (MMP-1) on regulating chemokine-dependent invasion of NK cells into type I collagen. We revealed that CXCL12 promoted the invasion program on freshly isolated human NK cells in a MAP kinase dependent manner, because CXCL12 enhanced NK cells invasion was significantly inhibited by p38MAP inhibitor SB203580 and MEK 1/2 inhibitor U0126. Next we examind whether CXCL12 especifically enhanced the production of MMP-1 from NK cells. This production wes significantly inhibited by SB203580 and U0126. Immunofluorescence confocal microscopic studies suggested that MMP-1 was co-localized with alpha2 integrin on the NK cell surface stimulated by CXCL12. The co-localization of MMP-1 and alpha2 integrin was significantly inhibited by SB203580 and U0126. Immunoprecipitation assy showd that productional MMP-1 associated with alpha2 beta1 integrin on NK cells stimulated by CXCL12. This association was significantly inhibited by SB203580 and U0126. These results suggested that MMP-1 associated with the cell surface was involved in NK cell invasion into type I collagen, and MMP-1 associated with alpha2 integrin on the cell surface may be a critical step in facilitating pericellular matrix degradation during cell invasion. [J Physiol Sci. 2006;56 Suppl:S117]
