Background: Cyclooxygenase (COX)-2 mRNA and protein expression have been found to be frequently up-regulated in human gastric cancers and cell lines. COX-2 is the inducible form of COX, and interleukin (IL)-1alpha may be one of the stimulators of COX-2.
Materials and methods: The relationship between IL-1alpha and COX-2 expression was examined in human gastric cancer tissues and cell lines.
Results: IL-1alpha mRNA was expressed in 19 out of 32 human gastric cancer specimens (60%), while it was not expressed in any of the paired normal gastric mucosa specimens. The incidence of IL-1alpha mRNA expression was significantly higher in patients with pT2-pT4 tumors than in those with pT1 tumors (86% vs. 39%, p<0.05). IL-1alpha mRNA was expressed in 94% of COX-2-positive tumors, while it was expressed in only 25% of COX-2-negative tumors (p<0.0001). When IL-1alpha was added to the medium of gastric cancer cell lines (MKN28 and MKN45), it enhanced the expression of IL-1alpha itself and COX-2 mRNA in both cell lines. Exogenous IL-1alpha stimulated cancer cell growth in both cell lines, while such growth stimulation was suppressed by anti-IL-1alpha antibody or IL-1 receptor antagonist. IL-1alpha-stimulated cell growth was also suppressed by anti-COX-2 antibody.
Conclusion: Our data demonstrated that IL-1alpha and COX-2 mRNA were frequently co-expressed in human gastric cancer tissues, and suggested that the IL-1alpha-COX-2 pathway might be involved in tumor progression by regulating cancer cell proliferation.