title: IL-23 directly enhances the proliferative and invasive activities of colorectal carcinoma.
abstract: Interleukin-23 (IL-23) plays an essential role in the mucosal immune system. It has been suggested that IL-23 is able to induce carcinogenesis as well as inflammation and a recent study revealed that IL-23R is expressed in colorectal carcinoma cells. However, neither the differences in the IL-23R expression among the patients nor the concrete functions of IL-23 in colorectal carcinoma cells have been revealed. The aim of the present study was to examine the characteristics of IL-23R expression in colorectal carcinoma and the direct effects of IL-23 on colorectal cancer cells. We examined the IL-23R expression in human colorectal cancer tissue samples by immunohistochemistry. Cell proliferation and invasion assays under IL-23 stimulation were performed using cultured cells derived from colorectal cancer. ELISA and real-time PCR were used to evaluate the transforming growth factor (TGF)-β production due to IL-23 stimulation. All of the TNM stage IV patients were positive for IL-23R. IL-23R expression in the carcinoma tissue was also relatively high at the deepest point of invasion in certain cases. The proliferative and invasive activities and/or TGF-β production of DLD-1 cells increased by IL-23 stimulation, whereas no change was observed in the activities of MIP101 and KM12c cells. IL-23 directly enhanced the malignancy of the colon carcinoma cells. An autocrine mechanism via TGF-β production may underlie these effects. IL-23 is therefore a potential target for cancer immunotherapy. However, the homogeneity in IL-23R expression and the effects of IL-23 on colorectal carcinoma cells should be considered.
authors: Division of Biological Regulation and Oncology, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-88574, Japan.
authors: Hideyuki
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authors: Suzuki
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authors: Sasaki