Effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum

In this experimental study, the effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum was investigated. A repr oducible in vitro assay was developed to study the adhesion of CC531 colon carcinoma cells to an autologous monolayer of rat mesothelial cells. Tumour cell adhesion to mesothelium pre-incubated with interleukin-1 beta (IL-1 b eta) and epidermal growth factor (EGF) resulted in at least 60% more tumour cell adhesion at maximal stimulation (p <0.001). Transforming growth facto r-beta (TGF-beta) pre-incubation resulted in minor, though significant stim ulation of cell adhesion (maximal 16%, p<0.05). The effect of IL-1<beta> wa s time- and dose-dependent. No mesothelial cell proliferation took place af ter pretreatment with IL-1 beta, indicating that enhanced adhesion was not based on an increase in the number of mesothelial cells. Pretreatment with EGF stimulated mesothelial cell growth as measured by DNA analysis. This ef fect on cell growth and adhesion was dose-dependent. Additional blocking ex periments with anti-IL-1 beta resulted in statistically significant inhibit ion of IL-1 beta -stimulated tumour cell adhesion (p less than or equal to0 .01), demonstrating the specificity of this effect. Interferon-gamma (IFN-g amma), tumour necrosis factor-alpha (TNF-alpha), IL-6, and insulin-like gro wth factor (IGF-I) pre-incubation had no effect on tumour cell adhesion, Th ese results prove that IL-1 beta and EGF are significant promoting factors in tumour cell adhesion to mesothelium in vitro and may therefore account f or tumour recurrence in the peritoneum in vivo. Copyright (C) 2001 John Wil ey & Sons, Ltd.