INTERLEUKIN-1 IS A MOTILITY FACTOR FOR HUMAN BREAST-CARCINOMA CELLS-INVITRO - ADDITIVE EFFECT WITH INTERLEUKIN-6

Interleukin-1beta (Il-1beta) and interleukin-1alpha (Il-1alpha) were shown to act as motility factors for the human breast carcinoma cell lines SK-BR-3 and ZR-75-1 in vitro. Both cytokines induced transition from the stationary to the motile phenotype (spreading). Il-1beta stimulated translocation, shape change and random migration (chemokinesis) of SK-BR-3 cells as demonstrated by time-lapse video recordings and by a modified Boyden chamber assay. Interleukin-6 (Il-6) stimulated spreading of the SK-BR-3 cells; an additive effect with Il-1beta on spreading and fast plasma membrane movements was evidenced. In the SK-BR-3 cell line, the signal transduction of Il-1beta and Il-6 differed, since only the effect of Il-6 on spreading was sensitive to pertussis toxin. Both Il-1beta and Il-6 required protein synthesis to stimulate spreading, since cycloheximide inhibited the effect of the cytokines. Induction of an autocrine loop of Il-6 in the SK-BR-3 cells by Il-1beta was unlikely, since after stimulation with Il-1beta, no induction of Il-6 activity was measured, nor was inhibition of stimulated spreading seen in the presence of an antiserum against Il-6. Addition of Il-8 or of an antiserum against Il-8 did not affect spreading. We concluded that Il-1 and Il-6 could act as motility factors for human breast carcinoma cells, in both an independent and an additive way. Human squamous cell carcinoma COLO-16 cells were found to secrete factors with similar effects on the SK-BR-3 and ZR-75-1 cells as the aforementioned cytokines. Although the presence of Il-1alpha and Il-6 activity in the COLO-16 conditioned medium was confirmed, a number of arguments were found to assume that still other factors beside these two cytokines were responsible for the motility-stimulating effect of the COLO-16 conditioned medium.