CXCL趋化因子家族在胃癌发生发展中的作用。
The role of CXCL chemokine family in the development and progression of gastric cancer.
作者信息
Chen Xuyan, Chen Renpin, Jin Ruifang, Huang Zhiming
机构信息
Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University Zhejiang, P. R. China.
出版信息
Int J Clin Exp Pathol. 2020 Mar 1;13(3):484-492. eCollection 2020.
The chemokine (C-X-C motif) ligand (CXCL) family plays an important role in inflammation. In order to understand the role of CXC chemokine family in carcinogenesis, this study explored a group of early gastric cancer (GC) patients, and assessed the level of CXC chemokine ligand (CXCL) in blood samples of patients representing systemic circulation and tumor microenvironment, detected the expression of CXC chemokine receptor (CXCR) in tumor tissues, and measured tumor infiltrating immune cell subsets. 69 patients with GC were included in a single center prospective study and were followed up for 6 years. The level of CXCL1-14 was determined by ELISA and the concentration gradient of chemokine was calculated. Western blot was used to detect the expression of CXCR1, CXCR2, CXCR3, and CXCR4 in tumor tissue. CXCL1-14 expression was inhibited by siRNA in HGC27 cells and then the migration ability of HGC27 cells was detected by cell scratch test. The results of this study showed that the chemokine concentrations of CXCL1, CXCL2, CXCL5, CXCL8, CXCL11, and CXCL13 in peripheral blood and tumor drainage blood of patients without recurrence after treatment were significantly lower than those before treatment. The concentrations of CXCL1, CXCL2, CXCL4, CXCL5, CXCL7, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13, and CXCL14 in peripheral blood and tumor drainage blood were significantly higher than those in patients without recurrence. Patients with low expression of CXCR1 and CXCR3 had lower AFP (alpha fetoprotein), smaller tumor volume, and lower TNM tumor stage. Patients with lower expression of CXCR2 and CXCR4 had higher AFP (alpha fetoprotein) level, larger tumor volume, and higher TNM tumor stage. After down-regulation of CXCLs expression, the migration ability of most cell lines was significantly inhibited. This study suggests that CXCL chemokine family plays an important role in the pathogenesis of GC and can be used as a marker for the development of GC.
趋化因子（C-X-C基序）配体（CXCL）家族在炎症中起重要作用。为了解CXC趋化因子家族在致癌作用中的作用，本研究对一组早期胃癌（GC）患者进行了探究，评估了代表全身循环和肿瘤微环境的患者血样中CXC趋化因子配体（CXCL）的水平，检测了肿瘤组织中CXC趋化因子受体（CXCR）的表达，并测定了肿瘤浸润免疫细胞亚群。69例GC患者纳入一项单中心前瞻性研究并随访6年。通过酶联免疫吸附测定法（ELISA）测定CXCL1-14的水平，并计算趋化因子的浓度梯度。采用蛋白质印迹法检测肿瘤组织中CXCR1、CXCR2、CXCR3和CXCR4的表达。在HGC27细胞中用小干扰RNA（siRNA）抑制CXCL1-14的表达，然后通过细胞划痕试验检测HGC27细胞的迁移能力。本研究结果显示，治疗后未复发患者外周血和肿瘤引流血中CXCL1、CXCL2、CXCL5、CXCL8、CXCL11和CXCL13的趋化因子浓度显著低于治疗前。外周血和肿瘤引流血中CXCL1、CXCL2、CXCL4、CXCL5、CXCL7、CXCL8、CXCL9、CXCL10、CXCL12、CXCL13和CXCL14的浓度显著高于未复发患者。CXCR1和CXCR3低表达的患者甲胎蛋白（AFP）水平较低、肿瘤体积较小且TNM肿瘤分期较低。CXCR2和CXCR4低表达的患者AFP水平较高、肿瘤体积较大且TNM肿瘤分期较高。CXCLs表达下调后，大多数细胞系的迁移能力受到显著抑制。本研究提示，CXCL趋化因子家族在GC发病机制中起重要作用，可作为GC进展的标志物。
Zotero 插件