Abstract 1334: Intratumoral soluble interleukin-6 receptor associated with disease progression in colorectal cancer

Abstract

Abstract Purpose. Interleukin-6 (IL-6) binds not only to membrane form but also to soluble IL-6 receptor (sIL-6R), derived from the extracellular part of the membrane receptor. Although most soluble receptors act as functional antagonists to their cytokine, sIL-6R plays a role in agonistic activity. The aim of this study was to clarify the relationship between concentration of intra-tumoral soluble interleukin-6 receptor levels and cancer progression in colorectal cancer patients, and to clarify its kinetics with clinical outcome. Methods. We studied 161 patients undergoing surgery for colorectal cancer. We measured concentrations of sIL-6R in tumors and normal mucosa, and in supernatants from colonic cancer cell lines. Expressions of IL-6, membranous IL-6R and gp130 were evaluated by immunohistochemically Results. The net balance between the concentration of sIL-6R in cancer tissue and normal mucosa (sIL-6R Ca/N expression ratio: the cancer tissue sIL-6R concentration divided by normal mucosa sIL-6Rntration) was 1.262 ± 1.156. The decreased sIL-6R Ca/N expression ratio was significantly associated with T classification (p=0.0076), distant metastasis (p=0.0102), UICC stage (p=0.0251) and poor prognosis (p=0.0003). In Cox multivariate analysis, distant metastasis and decreased sIL-6R Ca/N expression ratio were independent risk factors for poor prognosis. Colon cancer cell lines produced sIL-6R, and the production was exaggerated by IL-1beta stimulation, and was suppressed by the addition of IL-1 receptor antagonist. Immunohistochemically, IL-6, membranous IL-6R and gp130 were intensely expressed in cancer cell specifically, and IL-6 expression in cancer cytoplasm was associated with poor prognosis (p=0.0266). The decreased levels of sIL-6R Ca/N expression ratio in cancer tissue was inversely correlated with the intense IL-6 immunoreactivity in cancer cytoplasm (p=0.0088). Conclusion: Relative decrease in sIL-6R in the tumor stroma which reflects increased IL-6/sIL-6R affinity may play a key role in the progression of colorectal carcinoma via IL-6 tran-signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1334.