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Keywords:

interleukin-1, interleukin-6, motility, human breast carcinoma cells, cytokine interaction, tumor necrosis factor, growth-factor, human-melanoma, fibroblasts, interferon-beta-2, identification, purification, expression, movement, sequence, Science & Technology, Life Sciences & Biomedicine, Cell Biology, INTERLEUKIN-1, INTERLEUKIN-6, MOTILITY, HUMAN BREAST CARCINOMA CELLS, CYTOKINE INTERACTION, TUMOR NECROSIS FACTOR, GROWTH-FACTOR, HUMAN-MELANOMA, FIBROBLASTS, INTERFERON-BETA-2, IDENTIFICATION, PURIFICATION, EXPRESSION, MOVEMENT, SEQUENCE, Breast Neoplasms, Cell Membrane, Cell Movement, Cell Size, Culture Media, Conditioned, Cycloheximide, Drug Interactions, Female, Humans, Image Processing, Computer-Assisted, Interleukin-1, Interleukin-6, Pertussis Toxin, Recombinant Proteins, Tumor Cells, Cultured, Video Recording, Virulence Factors, Bordetella, 0601 Biochemistry and Cell Biology, 0607 Plant Biology, Developmental Biology, 3101 Biochemistry and cell biology, 3108 Plant biology

Abstract:

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.