Abstract
IL-6 is a multifunctional cytokine and involved in variety of carcinogenesis. However, the association between IL-6 and sporadic colorectal cancer has not been fully explained. Here, we investigated the role of IL-6 signaling and the cytokine network in sporadic colorectal cancer. We investigated the serum IL-6 levels in patients with sporadic colorectal adenoma, cancer patients, and normal controls. In addition, the expressions of IL-6, gp130, and the IL-6 receptor subunit were investigated in biopsy specimens collected from these subjects. Furthermore, the expressions of CXCL7 and CXCR2, a chemokine and its receptor involved in IL-6 production, were also investigated. We observed an elevated level of serum IL-6 in colorectal cancer patients and an increased expression of IL-6 in colorectal cancer tissues, compared with the levels in a control group and in patients with adenoma. The phosphorylation of gp130 was also increased in the colorectal cancer tissues, compared with that in control and adenoma tissues. The expressions of CXCL7 and CXCR2 in the colorectal cancer tissues were also higher than those in control and adenoma tissues. IL-6 signaling is involved in sporadic colorectal cancer. In addition, the increased expressions of CXCL7 and CXCR2 might, in turn, increase the expression of IL-6 in colorectal cancer. Further studies are required to elucidate the function of the IL-6 signaling and the cytokine network in sporadic colorectal cancer.
Highlights
Colorectal cancer is a major cause of mortality and morbidity worldwide [1], the mechanism of colorectal carcinogenesis remains unclear
The serum IL-6 level was significantly higher among the colorectal cancer patients than among the normal colorectal subjects or the adenoma patients (p < 0.05), no significant difference was observed between the normal colorectal subjects and the adenoma patients (Figure 1(a))
The mRNA expression of IL-6 was significantly higher in the colorectal cancer tissues than in the normal colorectal or adenoma tissues (p < 0.01)
Summary
Colorectal cancer is a major cause of mortality and morbidity worldwide [1], the mechanism of colorectal carcinogenesis remains unclear. Many studies have reported an association between interleukin-6 (IL-6) and colitis-associated cancer [2,3,4]. The association between IL-6 signaling and the sporadic colorectal adenoma-carcinoma sequence has not yet been clarified. IL-6 is a multifunctional cytokine important for immune response, cell survival, apoptosis and proliferation. IL-6 binds to soluble or membrane-bound IL-6 receptor (IL-6R) polypeptides that signal by interacting with the membrane-associated gp130 subunit, the engagement of which triggers the activation of Janus kinases (JAK)/STAT3 signaling [5]. Previous study showed that the interaction between mesenchymal stem cells and cancer stem cells is mediated by a positive feedback cytokine loop in which IL6 and CXCL7 play pivotal roles in vivo [6].
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