Migration of IL-2-activated natural killer cells in vitro: Influence of extracellular matrix proteins

An experimental set-up for estimating a) cellular migration under agarose and b) response to chemoattractant gradients built up in the agarose was used in order to explore the behavior of adherent interleukin-2 (IL-2)-activated natural killer (A-NK) cells on cell culture plastic and after coating with extracellular matrix (ECM) constituents. A-NK cells were deposited in wells in the agarose and directed migration, chemotaxis, towards aggregates and suspensions of B16F10 melanoma cells, suspensions of YAC-1 cells, and tumor-conditioned media, all deposited in wells at a 2.5 mm distance, was tested. A-NK cell chemotaxis was exclusively observed when B16F10 aggregates were used as attractants. The substrate influenced chemotaxis considerably, untreated plastic surface being most favorable for a chemotactic response, followed by laminin, fibronectin, and collagen IV pretreatments. Coating with reconstituted basement membrane matrix (Matrigel(R)) gave lesser random movements, chemokinesis, of A-NK cells than coating with the purified components laminin and collagen IS and the least motile response was obtained after collagen I pretreatment. These in vitro observations indicate that melanoma cell aggregates release humoral factors of a probably short-lived nature with a chemoattractant effect on A-NK cells, and that ECM composition influences migratory response, both conclusions with a bearing on the understanding of A-NK cell infiltration into tumors in vivo.