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 in human colon carcinoma specimens, in which it is tumour cell associated. In these experiments, IL-8 was shown to comprise an important component of the angiogenic activity of colon carcinoma cell line supernatants. The effect of modulating IL-8 activity upon the growth of the colon carcinoma cell lines HCT116A, HT29 and CaCo2 was investigated. Supplementing endogenously produced IL-8 by recombinant chemokine led to stimulation of cell growth. Neutralization of the effect of endogenously produced IL-8, either with the specific antagonist peptide AcRRWWCR or with blocking anti-IL-8 antibody, resulted in around 50% inhibition of cell growth (P<0.05). All of the colon carcinoma 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. Expression of IL-8RB was weak, although increased expression was seen in HCT116A cells as they approached confluence. Antibodies to IL-8RA and RB 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 support the concept that a similar autocrine loop operates in vivo.
Brew
R
R
Department of Immunology, University of Liverpool, Medical School, Daulby Street, Liverpool, L69 3GA, UK.
Erikson
J S
JS
West
D C
DC
Kinsella
A R
AR
Slavin
J
J
Christmas
S E
SE
D002277:Carcinoma / Q000098:blood supply / Q000276:immunology*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D016209:Interleukin-8; D012333:RNA, Messenger; D018123:Receptors, Interleukin