The possible role of factor H in colon cancer resistance to complement attack
The possible role of factor H in colon cancer resistance to complement attack
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DOI：
10.1002/ijc.23238
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发表时间：
2008-05-01
影响因子：
6.4
通讯作者：
Wilczynski, Grzegorz M.
中科院分区：
文献类型：
--
作者：
Wilczek, Ewa;Rzepko, Robert;Wilczynski, Grzegorz M.
近年来发现，可溶性补体抑制因子H(FH)及其剪接变异因子H样蛋白(FHL)在肺癌、卵巢肿瘤和神经胶质细胞肿瘤中发挥重要作用，使肿瘤细胞逃避补体介导的细胞毒。FH在结肠癌中的作用尚未被研究。在这里，我们研究了来自40例患者的肿瘤标本中FH/FHL的免疫细胞化学表达，这些患者既有原发性结肠腺癌，也有肝脏转移灶。FH/FHL免疫反应在原发灶和转移瘤的间质中均有表达，几乎在所有患者中都有表达。细胞免疫反应少见。重要的是，当进行定量分析时，与原发灶相比，肝转移灶中FH/FHL免疫反应性显著增加。此外，我们还分析了5种结肠癌细胞系SW480、SW620、HCT116、HT-29和LOVO中FH和FHL的表达。SW620和HT-29细胞有FH mRNA和FH分泌，而只有HT-29细胞才能产生FHL。在共聚焦显微镜和电子显微镜下，FH免疫反应与细胞膜和细胞内的囊泡结构有关。最后，我们分析了FH在SW620结肠癌细胞对补体介导的损伤易感性中的作用。当FH功能被阻断时，使用特异性抗体，细胞变得更容易溶解。综上所述，我们的结果提示FH/FHL在结肠癌细胞抵抗补体介导的细胞毒作用和转移过程中发挥着重要作用。(C)2008年Wiley-Liss，Inc.
A soluble complement inhibitor factor H (FH) and its splice variant factor H-like protein (FHL) have been recently discovered to play a major role in malignant cell escape from complement-mediated cytotoxicity in lung-, ovarian- and glia-derived neoplasms. The role of FH in colon cancer has not yet been examined. Here, we studied immunocytochemically FH/FHL expression in tumor samples derived from 40 patients, with both primary colon adenocarcinoma and metastatic foci in the liver. FH/FHL immunoreactivity was present in stroma of both primary and metastatic tumors, in virtually all patients. The cellular immunoreactivity was observed infrequently. Importantly, when analyzed quantitatively, FH/FHL immunoreactivity was significantly increased in liver metastases when compared with the primary sites. In addition, we have analyzed FH and FHL expression in 5 colon cancer cell lines: SW480, SW620, HCT116, HT-29 and Lovo. FH mRNA and FH secretion were observed in SW620 and HT-29 cells, whereas FHL was produced only by HT-29 cell-line. By confocal and electron microscopy, FH immunoreactivity was associated with the plasma membrane and intracellular vesicular structures. Finally, we have analyzed the role of FH in the susceptibility of SW620 colon cancer cells to complement-mediated damage. When FH function was blocked, using specific antibody, the cells became more susceptible to lysis. Taken together, our results suggest an important role of FH/FHL in colon cancer cells defense against complement-mediated cytotoxicity, and in metastatic process. (C) 2008 Wiley-Liss, Inc.