Li Xutong, Qian Dongmeng, Ju Fang, Wang Bin
Department of Microbiology, Medical College, Qingdao University, Qingdao, Shandong 266071, P.R. China ; Department of Oncology, Second Affiliated Hospital, Medical College, Qingdao University, Qingdao, Shandong 266042, P.R. China.
Department of Microbiology, Medical College, Qingdao University, Qingdao, Shandong 266071, P.R. China.
Oncol Lett. 2015 Jan;9(1):365-370. doi: 10.3892/ol.2014.2621. Epub 2014 Oct 15.
The aim of the present study was to investigate the association between Toll-like receptor 2 (TLR2) expression and human cytomegalovirus (HCMV) in colorectal carcinoma by detecting the expression of IE1-72, TLR2, TLR4 and tumor necrosis factor (TNF)-α in colorectal carcinoma and colon adenoma samples, as well as by analyzing the mRNA levels of the proteins in colon cancer cell lines, following HCMV infection. For this study, 56 colorectal cancer and 36 colon adenoma samples were collected, and normal mucosal tissue adjacent to the tumor was used as the control. The expression of the IE1-72, TLR2, TLR4, nuclear factor (NF)-κB and TNF-α protein was detected by immunohistochemistry. Cells from the SW480 human colon carcinoma cell line were infected with HCMV. The expression of IE1-72, TLR2, TLR4, NF-κB and TNF-α mRNA was quantified at different time points prior to and following infection. The positive expression rate of IE1-72 was 44.6% (25/56) in colorectal cancer and 41.7% (15/36) in colon adenoma. These rates were significantly higher when compared with the 12.5% (7/56) observed in the normal tissues adjacent to the cancer tissues (P<0.05). The expression levels of TLR2, TLR4, NF-κB and TNF-α in colorectal cancer and adenoma were also higher than those in the control tissues. Furthermore, the expression of IE1-72 in colorectal cancer tissues was found to correlate with TLR2 and TLR4, and the correlation coefficients were 0.515 and 0.462, respectively. Following the infection of SW480 cells, the mRNA levels of TLR2 and TNF-α increased gradually from 6 h, peaked at 48 h, and then decreased gradually. No significant differences in TLR4 and NF-κB expression were identified. The results of the present study indicated that there is a specific association between HCMV and the occurrence and development of colorectal cancer, which may be facilitated by the TLR2 signaling pathway.
本研究的目的是通过检测结直肠癌和结肠腺瘤样本中IE1-72、Toll样受体2(TLR2)、Toll样受体4(TLR4)和肿瘤坏死因子(TNF)-α的表达,以及分析人巨细胞病毒(HCMV)感染后结肠癌细胞系中这些蛋白的mRNA水平,来研究TLR2表达与HCMV在结直肠癌中的关联。本研究收集了56例结直肠癌和36例结肠腺瘤样本,并将肿瘤旁正常黏膜组织作为对照。采用免疫组织化学法检测IE1-72、TLR2、TLR4、核因子(NF)-κB和TNF-α蛋白的表达。用HCMV感染SW480人结肠癌细胞系。在感染前后的不同时间点对IE1-72、TLR2、TLR4、NF-κB和TNF-α mRNA的表达进行定量分析。结直肠癌中IE1-72的阳性表达率为44.6%(25/56),结肠腺瘤中为41.7%(15/36)。与癌旁正常组织中观察到的12.5%(7/56)相比,这些比率显著更高(P<0.05)。结直肠癌和腺瘤中TLR2、TLR4、NF-κB和TNF-α的表达水平也高于对照组织。此外,发现结直肠癌组织中IE1-72的表达与TLR2和TLR4相关,相关系数分别为0.515和0.462。SW480细胞感染后,TLR2和TNF-α的mRNA水平从6小时开始逐渐升高,在48小时达到峰值,然后逐渐下降。未发现TLR4和NF-κB表达有显著差异。本研究结果表明,HCMV与结直肠癌的发生发展之间存在特定关联,这可能由TLR2信号通路促成。