Dimberg Jan, Dienus Olaf, Löfgren Sture, Hugander Anders, Wågsäter Dick
Department of Natural Science and Biomedicine, University College of Health Sciences, SE-551 11 Jönköping, Sweden.
Int J Oncol. 2007 Jul;31(1):97-102.
Several studies indicate that chemokines play important roles in colorectal mucosal immunity by recruiting leukocytes into and out of the lamina propria adjacent to the epithelium. The chemokine CXCL5 which is expressed by epithelial cells within colorectal mucosa is a chemoattractant for neutrophils and has been implicated in Crohn's disease and ulcerative colitis. In addition, CXCL5 is one chemokine which promote angiogenesis related to cancer. The objective of this study was to determine by ELISA assay whether CXCL5 protein level is altered in colorectal cancer (CRC) tissues (n=80) compared with paired normal mucosa. Furthermore, the plasma CXCL5 levels from CRC patients (n=62) compared with controls (n=71) were also examined. Using a TaqMan system we screened for -156G--> C and +398G-->A CXCL5 gene variants in CRC patients (n=228) and a control group (n=231) to assess the role of CXCL5 genotype in CRC. The analyses showed that CXCL5 protein level in colorectal tumours was significantly (P<0.0001) higher than in normal tissue and was lower in plasma in CRC patients compared with controls (P=0.026). Immunohistochemistry revealed CXCL5 immunoreactivity mainly in epithelial cells of the colorectal carcinoma and in normal epithelial cells. Furthermore, patients who were -156C carriers had higher CXCL5 protein concentration compared with -156G carriers in normal tissue (P=0.027) and CXCL5 protein levels in cancerous tissue tended to be higher for the patient -156C carriers (P=0.059). To our knowledge this is the first report on the influence of CXCL5 gene variants and their relation to expression of CXCL5 protein in human CRC.
多项研究表明，趋化因子通过将白细胞招募到上皮相邻的固有层内外，在结肠直肠黏膜免疫中发挥重要作用。结肠直肠黏膜内的上皮细胞表达的趋化因子CXCL5是中性粒细胞的趋化剂，与克罗恩病和溃疡性结肠炎有关。此外，CXCL5是一种促进癌症相关血管生成的趋化因子。本研究的目的是通过酶联免疫吸附测定（ELISA）法确定与配对的正常黏膜相比，结肠直肠癌（CRC）组织（n = 80）中CXCL5蛋白水平是否发生改变。此外，还检测了CRC患者（n = 62）与对照组（n = 71）的血浆CXCL5水平。我们使用TaqMan系统在CRC患者（n = 228）和对照组（n = 231）中筛选了CXCL5基因-156G→C和+398G→A变体，以评估CXCL5基因型在CRC中的作用。分析表明，结肠直肠肿瘤中的CXCL5蛋白水平显著高于正常组织（P<0.0001），与对照组相比，CRC患者血浆中的CXCL5蛋白水平较低（P = 0.026）。免疫组织化学显示CXCL5免疫反应主要存在于结肠直肠癌的上皮细胞和正常上皮细胞中。此外，在正常组织中，-156C携带者患者的CXCL5蛋白浓度高于-156G携带者（P = 0.027），-156C携带者患者癌组织中的CXCL5蛋白水平往往更高（P = 0.059）。据我们所知，这是关于CXCL5基因变体对人类CRC的影响及其与CXCL5蛋白表达关系的首次报道。
