Interleukin-1 receptor antagonist inhibits the expression of vascular endothelial growth factor in colorectal carcinoma.

OBJECTIVE

Interleukin (IL)-1 is known to act as a tumor growth factor by inducing angiogenic factors. We examined the significance of IL-1beta 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-1beta in five colon cancer cell lines and the possible involvement of IL-1 RA. We also measured the tissue concentrations of IL-1beta, IL-1 RA and VEGF by ELISA in 65 colorectal cancer patients.

RESULTS

IL-1beta 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-1beta-induced VEGF secretion by 87%. Our data from the clinically obtained specimens showed that the IL-1 RA/IL-1beta ratio is significantly lower in cancer tissue. Regarding the clinicopathological parameters, the IL-1 RA/IL-1beta ratio was significantly lower in patients with vessel involvement than in those without involvement, and IL-1 RA/IL-1beta ratio was negatively correlated with the VEGF protein level in colorectal tumors.

CONCLUSIONS

Our data suggest that IL-1beta induces VEGF expression and IL-1 RA acts as the competitive inhibitor, and that the IL-1 RA/IL-1beta ratio is significant for VEGF expression in the microenvironment of colorectal cancer tissue. We conclude that IL-1beta 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.