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

被引:72
作者
Grimm, Martin [1 ]
Kim, Mia [1 ]
Rosenwald, Andreas [2 ]
Heemann, Uwe [3 ]
Germer, Christoph-Thomas [1 ]
Waaga-Gasser, Ana Maria [1 ]
Gasser, Martin [1 ]
机构
[1] Univ Wurzburg, Dept Surg 1, D-97080 Wurzburg, Germany
[2] Univ Wurzburg, Inst Pathol, D-97080 Wurzburg, Germany
[3] Univ Munich, Dept Nephrol, Klinikum Rechts Isar, Munich, Germany
关键词
Colorectal cancer progression; Toll-like receptor; Inflammation; Tumour-initiating cells; HELICOBACTER-PYLORI; CYCLOOXYGENASE-2; CHEMORESISTANCE; CARCINOGENESIS; CARCINOMA; PATHWAY; LINK;
D O I
10.1016/j.ejca.2010.07.017
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2849 / 2857
页数:9
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