Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Br J Cancer. 2010 Sep 7;103(6):787-95. doi: 10.1038/sj.bjc.6605827.
Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients.
We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis.
Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio <1.0 was significantly associated with factors reflecting disease progression, and was an independent prognostic factor not only in all the patients in this study, but also in the patients with curative intent. Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation. Immunohistochemistry revealed that loss of tumour expression of sIL-6R was significantly inversely correlated with intense IL-6 expression in the cytoplasm of cancer cells. In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.
Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.
白细胞介素 6（IL-6）与 IL-6 受体的膜结合形式和可溶性形式（sIL-6R）结合，后者诱导与 gp130 的复合物，并促进肿瘤细胞增殖。本研究旨在阐明结直肠癌患者肿瘤中 sIL-6R 的表达与疾病进展之间的关系。
我们测量了 161 例接受手术的结直肠癌患者肿瘤和正常黏膜中的 sIL-6R 组织浓度，以及结肠癌细胞系的上清液中的 sIL-6R 浓度。通过免疫组织化学分析评估了 IL-6、IL-6R 和 gp130 的表达。
肿瘤中 sIL-6R 的表达缺失（定义为 sIL-6R Ca/N 比<1.0）与反映疾病进展的因素显著相关，并且是独立的预后因素，不仅在本研究中的所有患者中如此，而且在有治愈意向的患者中也是如此。结肠癌细胞系在体外产生 sIL-6R，细胞因子刺激可刺激癌细胞系中 sIL-6R 的产生。免疫组织化学显示，肿瘤中 sIL-6R 的表达缺失与癌细胞胞质中 IL-6 的强烈表达呈显著负相关。此外，肿瘤中 IL-1β的表达与 sIL-6R 的表达显著相关。
肿瘤中 sIL-6R 的表达缺失与结直肠癌的疾病进展有关。
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