Interleukin-1 Receptor Antagonist Inhibits the Expression of Vascular Endothelial Growth Factor in Colorectal Carcinoma

Abstract

Objective: Interleukin (IL)-1 is known to act as a tumor growth factor by inducing angiogenic factors. We examined the significance of IL-1β and IL-1 receptor antagonist (RA) for inducing the expression of vascular endothelial growth factor (VEGF) in colorectal cancers. Methods: We investigated the expression of VEGF induced by IL-1β in five colon cancer cell lines and the possible involvement of IL-1 RA. We also measured the tissue concentrations of IL-1β, IL-1 RA and VEGF by ELISA in 65 colorectal cancer patients. Results: IL-1β induced VEGF secretion with a 19-fold increase in Caco-2 cells. A significant increase in VEGF secretion was also observed in SW480 and WiDr cells. IL-1 RA inhibited IL-1β-induced VEGF secretion by 87%. Our data from the clinically obtained specimens showed that the IL-1 RA/IL-1β ratio is significantly lower in cancer tissue. Regarding the clinicopathological parameters, the IL-1 RA/IL-1β ratio was significantly lower in patients with vessel involvement than in those without involvement, and IL-1 RA/IL-1β ratio was negatively correlated with the VEGF protein level in colorectal tumors. Conclusions: Our data suggest that IL-1β induces VEGF expression and IL-1 RA acts as the competitive inhibitor, and that the IL-1 RA/IL-1β ratio is significant for VEGF expression in the microenvironment of colorectal cancer tissue. We conclude that IL-1β induces VEGF secretion in a certain population of colorectal cancer patients, and that IL-1 RA is the potential therapeutic agent for antiangiogenic therapy in colorectal cancer patients.