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

Cytokine. 2000 Jan;12(1):78-85. doi: 10.1006/cyto.1999.0518.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / blood supply
  • Carcinoma / immunology*
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Growth Substances / genetics
  • Growth Substances / metabolism*
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Neovascularization, Pathologic / immunology*
  • RNA, Messenger / analysis
  • Receptors, Interleukin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Growth Substances
  • Interleukin-8
  • RNA, Messenger
  • Receptors, Interleukin