Role of CXCL12 in metastasis of human ovarian cancer

作     者：JIANG Yu-ping WU Xiao-hua XING Han-ying DU Xing-yan 

作者机构：Department of Obstetrics and Gynecology Second Hospital of Hebei Medical University Shijiazhuang 050000 China Department of Obstetrics and Gynecology Second Hospital of Hebei Medical University Shijiazhuang 050011 China Clinical Medical Research Center Hebei General Hospital Shijiazhuang 050000 China Department of Haematology Fourth Hospital of Hebei Medical University Shijiazhuang 050000 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2007年第120卷第14期

页      面：1251-1255页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：National Research Foundation Singapore 

主　　题：ovarian cancer metastasis CXCL12 

摘      要：Background In a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explore the effect of CXCL12-CXCR4 axis on the metastasis of human ovarian cancer. Methods The expressions of CXCR4 and CXCL12 mRNA and protein in human ovarian cancer cell line CAOV-3 was detected by RT-PCR and immunocytochemistry. *** （MTT） was used to analyze the effect of different concentrations of CXCL12 on the proliferation of CAOV-3 cells. Transwell invasion chamber and matrigel were used to evaluate the effect of various concentrations of CXCL12 and ascites on the migration and invasion of CAOV-3 cells. The expressions of integrin β1 and vascular endothelial growth factor-C （VEGF-C） mRNA were detected by RT-PCR. Data were analyzed using ANOVA by SAS 6.12. Results Under serum-free suboptimal culture conditions, CXCL12 （100 ng/ml） significantly enhanced the proliferation of CAOV-3 cells compared with the control and 10 ng/ml CXCL12 groups （0.428 ± 0.051 vs. 0.325 ±0.045 and 0.328±0.039, P〈0.05）. This enhancing effect of CXCL12 was significantly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml CXCR4 antagonist AMD3100. However, 10 μg/ml neutralizing CXCR4 antibody could not inhibit cell proliferation without CXCL12. The levels of migration and invasion of the CAOV-3 cells treated with 100 ng/ml CXCL12 were significantly higher than those in the control （migration： 523.3± 25.2 vs 108.0 ± 7.2; invasion： 39.3 ± 4.0 vs. 4.0 ± 1.0）. The enhancing effect of CXCL12 on cell migration and invasion increased with the concentration of CXCL12 （100 ng/ml vs 10 ng/ml： migration, 523.3 ± 25.2 vs 211.7 ± 24.7; invasion, 39.3 ± 4.0 vs 15.7 ± 3.1, P〈0.05）, and was strongly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml AMD3100. The number of migrated and invading cells in the CAOV-3 added with ascites was significantl