Interleukin-8 as an autocrine growth factor for human colon carcinoma cells in vitro

Cell lines derived from human colon carcinomas secrete interleukin 8 (IL-8) in vitro and this chemokine has also been detected immunohistochemically i n human colon carcinoma specimens, in which it is tumour cell associated. I n these experiments, IL-8 was shown to comprise an important component of t he angiogenic activity of colon carcinoma cell line supernatants, The effec t of modulating IL-8 activity upon the growth of the colon carcinoma cell l ines HCT116A, HT29 and CaCo2 was investigated. Supplementing endogenously p roduced IL-8 by recombinant chemokine led to stimulation of cell growth. Ne utralization of the effect of endogenously produced IL-8, either with the s pecific antagonist peptide AcRRWWCR or with blocking anti-IL-8 antibody, re sulted in around 50% inhibition of cell growth (P<0.05). All of the colon c arcinoma cell lines tested expressed mRNA for both IL-8RA and RB when grown at:confluence. At the protein level, all cell lines expressed IL-8RA, Expr ession of IL-8RB was weak, although increased expression was seen in HCT116 A cells as they approached confluence, Antibodies to IL-8RA and RE did not affect proliferation at low cell density but were strongly inhibitory when cells were cultured at a higher density. These data suggest that IL-8 acts as an autocrine growth factor for colon carcinoma cell lines and would supp ort the concept that a similar autocrine loop operates in vivo. (C) 2000 Ac ademic Press.