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 reproducible 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-1beta (IL-1beta) and epidermal growth factor (EGF) resulted in at least 60% more tumour cell adhesion at maximal stimulation (p</=0.001). Transforming growth factor-beta (TGF-beta) pre-incubation resulted in minor, though significant stimulation of cell adhesion (maximal 16%, p<0.05). The effect of IL-1beta was time- and dose-dependent. No mesothelial cell proliferation took place after pretreatment with IL-1beta, 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 effect on cell growth and adhesion was dose-dependent. Additional blocking experiments with anti-IL-1beta resulted in statistically significant inhibition of IL-1beta-stimulated tumour cell adhesion (p</=0.01), demonstrating the specificity of this effect. Interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IL-6, and insulin-like growth factor (IGF-I) pre-incubation had no effect on tumour cell adhesion. These results prove that IL-1beta and EGF are significant promoting factors in tumour cell adhesion to mesothelium in vitro and may therefore account for tumour recurrence in the peritoneum in vivo.
Laboratory for Experimental Surgery and Oncology, Erasmus University Rotterdam, Dr Molewaterplein 50, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
M E
ME
van Rossen
L J
LJ
Hofland
M P
MP
van den Tol
P M
PM
van Koetsveld
J
J
Jeekel
R L
RL
Marquet
C H
CH
van Eijck
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003110:Colonic Neoplasms / Q000473:pathology*; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006133:Growth Substances / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000494:pharmacology; D008297:Male; D009366:Neoplasm Seeding; D010537:Peritoneum / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D016207:Cytokines; D006133:Growth Substances; D018836:Inflammation Mediators