共 24 条
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
相关论文