Department of Laryngology and Laryngological Oncology, Medical University of Lodz, Poland.
Adv Med Sci. 2012 Jun 1;57(1):124-35. doi: 10.2478/v10039-011-0058-3.
The aim of this study was to analyze of TLRs mRNA expression in peripheral blood mononuclear cells as potential biomarkers of neoplastic lesions progress and to evaluate their role in the possible mechanisms responsible for the secretion of cytokines in laryngeal cancer.
MATERIAL/METHODS: The analysis of TLR2, TLR4, TRAF6, IRAK1 expression in isolated PBMCs by the reverse transcription PCR (RT-PCR) analysis as well as IL-6, IL-8 and TNF-α levels in supernatants of peripheral blood mononuclear cells from 55 patients with carcinoma of the larynx was performed by ELISA. The invasiveness of carcinoma was evaluated according to tumor front grading, TFG.
We noted that tumors with a well-defined borderline were characterized by significantly higher values of the average expression of TRAF6. Our research also confirmed that more aggressive carcinomas according to TFG, with a more dispersed type of invasion were characterized by significantly lower values of the average expression of IRAK1. Moreover, we observed that tumors with the invasion of cartilage were characterized by significantly lower values of the average expression of TLR4. In addition, the relationships of TLR2 with IL-6 and TNF-α level were highlighted. Significant interconnections were also found between the TLR4 and IL-8, TNF-α, IL-6 secretion after stimulation. The relationships of TRAF6 with IL-8 production after stimulation were noted.
Our findings confirmed the implication of the TLRs pathway molecules in proinflammatory cytokine secretions and their importance as encouraging potential indicators for assessment of the degree of aggressive tumor phenotype.
本研究旨在分析外周血单个核细胞中 TLRs mRNA 的表达,作为肿瘤病变进展的潜在生物标志物,并评估其在喉癌中可能负责细胞因子分泌的机制中的作用。
材料/方法:通过逆转录 PCR(RT-PCR)分析,对分离的 PBMC 中的 TLR2、TLR4、TRAF6、IRAK1 表达进行分析,并通过 ELISA 检测 55 例喉癌患者外周血单个核细胞上清液中 IL-6、IL-8 和 TNF-α 的水平。根据肿瘤前缘分级(TFG)评估癌的侵袭性。
我们注意到,边界明确的肿瘤 TRAF6 平均表达值明显较高。我们的研究还证实,根据 TFG,侵袭性更强、侵袭方式更分散的癌具有明显较低的 IRAK1 平均表达值。此外,我们观察到,软骨侵袭的肿瘤 TLR4 平均表达值明显较低。此外,还强调了 TLR2 与 IL-6 和 TNF-α 水平之间的关系。还发现了 TLR4 与刺激后 IL-8、TNF-α、IL-6 分泌之间的显著相互关系。还注意到 TRAF6 与刺激后 IL-8 产生之间的关系。
我们的研究结果证实了 TLRs 途径分子在促炎细胞因子分泌中的作用,以及它们作为评估肿瘤侵袭性表型程度的潜在有价值指标的重要性。