The Decoy Receptor Interleukin-1 Receptor Type 2 Acts As An Angiogenic Factor In Human Colorectal Cancer

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAWe previously demonstrated that interleukin-1 receptor type 2 (IL1R2), an IL-1 decoy receptor that inhibits exogenous IL-1 signaling, intracellularly activates the expression of several pro-inflammatory cytokines. In this study, we observed that IL1R2 was overexpressed in human colon cancer cells (CRC) compared to normal colon cells. In addition, we observed that the IL1R2 level was higher in late-stage clinical CRC patients and that a high level of IL1R2 was associated with a poor 5-year survival rate in CRC patients. Furthermore, we observed that the levels of IL1R2 and IL-6 were strongly correlated in 40 CRC patients. To elucidate the oncogenic roles of intracellular IL1R2, we modulated its expression levels in human CRC cell lines. We verified that the intracellular level of IL1R2 was correlated with the migration ability of CRC, cells. We observed that the VEGF-A and IL-6 levels were significantly increased in conditioned media harvested from IL1R2-overexpressing cells, and these elevated VEGF-A and IL-6 levels enhanced the proliferation, migration, and tube formation of cultured endothelial cells. We further demonstrated that intracellular IL1R2 levels were positively associated with tumor growth and microvessel density in xenograft mouse models. Furthermore, we observed that IL1R2 formed a complex with c-Fos. This complex bound to the AP-1 site at the IL-6 and VEGF-A promoters. Together, these results reveal that intracellular IL1R2 acts with c-Fos to enhance the transcription of IL-6 and VEGF-A, which promotes tumor malignancy and angiogenesis.Citation Format: Ai-Chung Mar. The decoy receptor interleukin-1 receptor type 2 acts as an angiogenic factor in human colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1361. doi:10.1158/1538-7445.AM2015-1361