Laboratory for Immunology and Hematology Research, Rabin Medical Center-Hasharon Hospital, Petah-Tiqva and the Sackler School of Medicine, Tel-Aviv University, 7 Keren Kayemet St., Ramat-Aviv, Israel.
Biomed Pharmacother. 2010 Dec;64(10):706-11. doi: 10.1016/j.biopha.2010.08.006. Epub 2010 Sep 9.
Patients with ulcerative colitis and Crohn's disease are at increased risk for colorectal cancer, a phenomenon assumed to be at least in part consequence of chronic inflammation. The purpose of this study was to examine whether human colon cancer cells may promote immune cells to produce cytokines, particularly those involved in inflammatory reaction. HT-29 and RKO human colon cancer cell lines were used. Human peripheral blood mononuclear cells (PBMC) were incubated for 24 h without or with cancer cells, or with supernatants derived from these cells cultured at the same conditions. TNFα, IL-1β, IL-6, IFNγ, IL-1ra and IL-10 secreted by PBMC were detected using specific ELISA kits. Interaction between colon cancer cells and PBMC induced secretion of pro- and anti-inflammatory cytokines in a dose-dependent manner. Furthermore, supernatants from increasing number of colon cancer cells caused a dose-dependent cytokine secretion. However, the production of cytokines was more pronounced when PBMC were directly exposed to tumor cells as compared to their supernatants. The results of our experimental model demonstrating an altered balance between pro- and anti-inflammatory cytokines generated by interaction between colon cancer and immune cells support the role of the malignant cells in promoting inflammation as one of the mechanisms for progression of colon cancer.
溃疡性结肠炎和克罗恩病患者罹患结直肠癌的风险增加，这种现象至少部分归因于慢性炎症。本研究旨在探讨人结肠癌细胞是否能促使免疫细胞产生细胞因子，特别是那些参与炎症反应的细胞因子。使用 HT-29 和 RKO 人结肠癌细胞系。将人外周血单核细胞（PBMC）在无癌细胞或与相同条件下培养的这些细胞的上清液存在的情况下孵育 24 小时。使用特定的 ELISA 试剂盒检测 PBMC 分泌的 TNFα、IL-1β、IL-6、IFNγ、IL-1ra 和 IL-10。结肠癌细胞与 PBMC 的相互作用以剂量依赖性方式诱导促炎和抗炎细胞因子的分泌。此外，随着结肠癌细胞数量的增加，细胞因子的分泌也呈剂量依赖性。然而，与仅暴露于肿瘤细胞的上清液相比，当 PBMC 直接暴露于肿瘤细胞时，细胞因子的产生更为明显。我们的实验模型结果表明，结肠癌细胞与免疫细胞相互作用产生的促炎和抗炎细胞因子之间的平衡发生改变，支持恶性细胞在促进炎症方面的作用，这是结肠癌进展的机制之一。
