Suzuki Hideyuki, Ogawa Hitoshi, Miura Koh, Haneda Sho, Watanabe Kazuhiro, Ohnuma Shinobu, Sasaki Hiroyuki, Sase Tomohiko, Kimura Shunichi, Kajiwara Taiki, Komura Toshihiro, Toshima Masahide, Matsuda Yasufumi, Shibata Chikashi, Sasaki Iwao
Division of Biological Regulation and Oncology, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-88574, Japan.
Oncol Lett. 2012 Aug;4(2):199-204. doi: 10.3892/ol.2012.739. Epub 2012 May 30.
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.
白细胞介素-23（IL-23）在黏膜免疫系统中发挥着重要作用。有人提出IL-23能够诱导癌变以及炎症，并且最近一项研究显示IL-23受体（IL-23R）在结肠癌细胞中表达。然而，患者之间IL-23R表达的差异以及IL-23在结肠癌细胞中的具体功能均未被揭示。本研究的目的是检测结肠直肠癌中IL-23R表达的特征以及IL-23对结肠癌细胞的直接作用。我们通过免疫组织化学检测了人结肠直肠癌组织样本中的IL-23R表达。使用源自结肠直肠癌的培养细胞进行了IL-23刺激下的细胞增殖和侵袭试验。采用酶联免疫吸附测定（ELISA）和实时聚合酶链反应（PCR）来评估IL-23刺激引起的转化生长因子（TGF）-β产生。所有TNM分期为IV期的患者IL-23R均呈阳性。在某些病例中，癌组织中IL-23R的表达在侵袭最深点也相对较高。IL-23刺激可增加DLD-1细胞的增殖和侵袭活性以及/或TGF-β产生，而MIP101和KM12c细胞的活性未观察到变化。IL-23直接增强了结肠癌细胞的恶性程度。通过TGF-β产生的自分泌机制可能是这些作用的基础。因此，IL-23是癌症免疫治疗的一个潜在靶点。然而，应考虑IL-23R表达的同质性以及IL-23对结肠癌细胞的作用。
