Li Ying-Ying, Hsieh Ling-Ling, Tang Rei-Ping, Liao Shuen-Keui, Yeh Kun-Yun
Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung & Chang Gung University, Taiwan.
Cell Immunol. 2009;256(1-2):19-26. doi: 10.1016/j.cellimm.2009.01.001. Epub 2009 Feb 7.
Little is known regarding the effects of IL-6 released by tumor-infiltrating macrophages on the mucin expression of colon cancer cells. We isolated macrophages from healthy donors and harvested the supernatant after 48-h cultures. Using flow cytometry and intracellular staining methods, we found that macrophage supernatant effectively induced MUC1 up-regulation and MUC2 down-regulation of colon cancer cells in vitro. Western blotting analysis using monoclonal antibody against IL-6 or gp 130 verified that this IL-6-driven activity was through the activation of tyrosine phosphorylation (Tyr(705)) of STAT3 in cancer cells. We analyzed the surgical specimens of 29 patients with colon cancer by an immunohistochemical staining method and demonstrated the co-localization of macrophages, and the expression of IL-6, CD68, and MUC1 in colon cancer patients. Therefore, macrophage-derived IL-6 modulates the mucin expression of colorectal cancer cells that might in turn produce a permissive milieu favorable to cancer spread.
关于肿瘤浸润巨噬细胞释放的白细胞介素-6（IL-6）对结肠癌细胞黏蛋白表达的影响，目前所知甚少。我们从健康供体中分离出巨噬细胞，并在培养48小时后收集上清液。使用流式细胞术和细胞内染色方法，我们发现巨噬细胞上清液在体外能有效诱导结肠癌细胞的MUC1上调和MUC2下调。使用抗IL-6或gp130的单克隆抗体进行的蛋白质印迹分析证实，这种由IL-6驱动的活性是通过激活癌细胞中信号转导和转录激活因子3（STAT3）的酪氨酸磷酸化（Tyr(705)）实现的。我们通过免疫组织化学染色方法分析了29例结肠癌患者的手术标本，证实了巨噬细胞、IL-6、CD68和MUC1在结肠癌患者中的共定位。因此，巨噬细胞衍生的IL-6调节结肠癌细胞的黏蛋白表达，这可能反过来产生有利于癌症扩散的宽松环境。
