Toll-like receptor (TLR) 7 and TLR8 expression on CD133+ cells in colorectal cancer points to a specific role for inflammation-induced TLRs in tumourigenesis and tumour progression
Toll-like receptor (TLR) 7 and TLR8 expression on CD133+ cells in colorectal cancer points to a specific role for inflammation-induced TLRs in tumourigenesis and tumour progression
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DOI：
10.1016/j.ejca.2010.07.017
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发表时间：
2010-10-01
影响因子：
8.4
通讯作者：
Gasser, Martin
中科院分区：
文献类型：
--
作者：
Grimm, Martin;Kim, Mia;Gasser, Martin
Toll样受体（TLR）刺激导致NF-κ B的活化，NF-κ B是驱动炎症至癌症的关键调节剂，并且有丝分裂原活化蛋白激酶已显示在致癌作用中募集有丝分裂和环氧合酶-2（考克斯-2）诱导的途径。在这里，我们问不同的TLR，考克斯-2和干细胞标志物的表达谱在结直肠癌（CRC）提供进一步的证据，从临床的角度来看，这一假设。我们分析了TLR 7-TLR 10、考克斯-2和CD 133的基因和蛋白表达，作为CRC患者（n = 65）中结肠起始细胞的标志物。基因分析显示，在CRC肿瘤组织中TLR 7-TLR 10和考克斯-2的表达显著上调。从原发性肿瘤中分离的肿瘤细胞的分析显示TLR 7和TLR 8与CD 133共表达，并提供了结肠癌起始细胞亚群的证据。在多变量分析中，发现TLR 8表达是一个独立的预后因素。因此，CRC中，特别是肿瘤起始细胞中NF-κ B的持续TLR特异性激活可能通过已知的炎症和组织修复机制的永久信号传导以及多能肿瘤细胞中的连续自我更新来维持进一步的肿瘤生长和进展。通过自身配体或病毒RNA片段的激活可能会维持这种炎症过程，表明在癌症进展中的关键作用。(c)2010爱思唯尔有限公司版权所有。
Toll-like receptor (TLR) stimulation results in activation of NF-kappa B, a key modulator in driving inflammation to cancer and mitogen-activated protein kinases that have been shown to recruit mitotic and cyclooxygenase-2 (COX-2) induced pathways in carcinogenesis. Here we asked whether different TLR, COX-2 and stem cell marker expression profiles in colorectal cancer (CRC) provide further evidence for this hypothesis from a clinical perspective. We analysed gene and protein expression of TLR7-TLR10, COX-2 and CD133 as a marker for colon-initiating cells in CRC patients (n = 65). Gene analysis demonstrated significantly upregulated TLR7-TLR10 and COX-2 expression in CRC tumour tissues. Analysis of isolated tumour cells from primary tumours showed co-expression of TLR7 and TLR8 with CD133 and gave evidence for a subpopulation of colon cancer-initiating cells. In multivariate analyses TLR8 expression was found to be an independent prognostic factor. Persistent TLR-specific activation of NF-kappa B in CRC and particularly in tumour-initiating cells may thus sustain further tumour growth and progression through perpetuated signalling known from inflammatory and tissue repair mechanisms with consecutive self-renewal in pluripotent tumour cells. Activation through self-ligands or viral RNA fragments may putatively maintain this inflammatory process, suggesting a key role in cancer progression. (c) 2010 Elsevier Ltd. All rights reserved.