MIGRATION OF IL-2-ACTIVATED NATURAL-KILLER-CELLS IN-VITRO - INFLUENCEOF EXTRACELLULAR-MATRIX PROTEINS

An experimental set-up for estimating a) cellular migration under agar ose and b) response to chemoattractant gradients built up in the agaro se 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 c ells were deposited in wells in the agarose and directed migration, ch emotaxis, towards aggregates and suspensions of B16F10 melanoma cells, suspensions of YAC-1 cells, and tumor-conditioned media, all deposite d 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 su rface being most favorable for a chemotactic response, followed by lam inin, fibronectin, and collagen IV pretreatments. Coating with reconst ituted basement membrane matrix (Matrigel(R)) gave lesser random movem ents, chemokinesis, of A-NK cells than coating with the purified compo nents laminin and collagen IS and the least motile response was obtain ed after collagen I pretreatment. These in vitro observations indicate that melanoma cell aggregates release humoral factors of a probably s hort-lived nature with a chemoattractant effect on A-NK cells, and tha t ECM composition influences migratory response, both conclusions with a bearing on the understanding of A-NK cell infiltration into tumors in vivo.