Abstract
The occurrence and development of colon cancer is closely related to inflammation. Thus, we conducted the present retrospective study to investigate the effects of IL-37 (Interleukin 37), a newly identified anti-inflammatory factor, on colon cancer development. We first evaluated the IL-37 expression in 186 pairs of colon cancer samples and their adjacent normal mucosa by real-time PCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-37 on patient survival rates, colon cancer progression and their sensitivity to chemotherapy drugs were assessed. IL-37 was barely expressed in the colon cancer tissue but highly expressed in the adjacent normal tissue. The down-regulation of IL-37 was significantly correlated with the results of American Joint Committee on Cancer stage, nodal involvement, invasion depth, distant metastasis, differentiation and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with colon cancer. Overexpression of IL-37 in colon cancer cell suppressed cell migration, invasion, proliferation, colony formation and cancer stem cells through suppressing β-catenin. IL-37 inhibited colon tumor formation in the mice model and sensitize the cancer cell to chemotherapy drugs. Our results showed that IL-37 plays an inhibitory role in colon cancer development and function as a novel prognostic indicator and a potential therapeutic target.
Highlights
Colon cancer is one of the most prevalent malignancies worldwide [1]
The down-regulation of IL-37 was significantly correlated with the results of American Joint Committee on Cancer stage, nodal involvement, invasion depth, distant metastasis, differentiation and it was shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with colon cancer
Our results showed that IL-37 plays an inhibitory role in colon cancer development and function as a novel prognostic indicator and a potential therapeutic target
Summary
It is estimated that over half of the colon cancer patients had developed distant metastasis [2]. Previous studies have demonstrated that multiple mechanisms are responsible for the colon cancer development. Growing evidences indicate that immune mechanisms are important in colon cancer progression [4]. Pro-inflammatory cytokines are related to tumor development, including proliferation, metastasis, apoptosis and angiogenesis [5]. It has been demonstrated that IL-37 suppresses tumor progression, including cervical cancer [9], fibrosarcoma [10], hepatocellular carcinoma [11], lung cancer [12, 13], renal cell carcinoma[14] and breast cancer [15]. Whether IL-37 shows anti-tumor effects in colon cancer remains unknown. We investigated the role of IL-37 in colon cancer in the current study
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