Rebollo Juan, Geliebter Jan, Reyes Niradiz
Research group of Genetics and Molecular Biology. School of Medicine. University of Cartagena. Colombia.
Graduate School of Basic Medical Sciences. New York Medical College. Valhalla, NY, United States.
Int J Biomed Sci. 2017 Mar;13(1):35-42.
Endothelial cell-specific molecule-1 (ESM-1), also known as endocan, is a soluble proteoglycan expressed by the vascular endothelium, which also circulates in the bloodstream. Inflammatory cytokines and proangiogenic growth factors increase its expression, and increased serum levels have been reported in several cancer types and immunocompetent patients with sepsis. The aim of this study was to analyze the expression profile of CXC-chemokines and the effects of ESM-1 gene knockdown in proliferation, migration and CXC-chemokine expression in highly metastatic human prostate PC-3 cells. Expression profiles of CXC-chemokines were analyzed in metastatic PC-3 and non-tumorigenic PWR-1E cells. siRNA-mediated knockdown of ESM-1 was performed into PC-3 cells, which were subsequently tested for cell migration and proliferation. Effect of siRNA transfection on CXC-chemokine expression was further quantified at the transcript and protein level. RT-qPCR analysis and sandwich ELISA assay revealed higher levels of ESM-1 and several CXC-chemokines in metastatic PC-3 cells compared to non-tumorigenic PWR-1E. Transfection of PC-3 cells with ESM-1-siRNA decreased cell migration with no effect on proliferation, and it was accompanied by decrease in the transcript and protein levels of the angiogenic chemokine CXCL3. We report here for the first time the ESM-1 targeting in PC-3 cells, which resulted in decreased migration, which may be related, at least in part, to decreased expression of the angiogenic CXCL3 chemokine, whose expression was found to be reduced in ESM-1-siRNA transfected cells. Additional studies are required to ascertain the biological role of ESM-1 in prostate cancer cells and the link with the expression of CXCL3.
内皮细胞特异性分子-1(ESM-1),也称为内皮糖蛋白,是一种由血管内皮表达的可溶性蛋白聚糖,它也在血液中循环。炎性细胞因子和促血管生成生长因子会增加其表达,并且在几种癌症类型以及患有败血症的免疫功能正常的患者中,血清水平均有升高的报道。本研究的目的是分析CXC趋化因子的表达谱以及ESM-1基因敲低对高转移性人前列腺PC-3细胞增殖、迁移和CXC趋化因子表达的影响。在转移性PC-3细胞和非致瘤性PWR-1E细胞中分析了CXC趋化因子的表达谱。对PC-3细胞进行了小干扰RNA(siRNA)介导的ESM-1敲低,随后检测这些细胞的迁移和增殖情况。进一步在转录水平和蛋白质水平定量分析了siRNA转染对CXC趋化因子表达的影响。逆转录定量聚合酶链反应(RT-qPCR)分析和夹心酶联免疫吸附测定(ELISA)显示,与非致瘤性PWR-1E细胞相比,转移性PC-3细胞中ESM-1和几种CXC趋化因子的水平更高。用ESM-1-siRNA转染PC-3细胞可降低细胞迁移,对增殖无影响,同时血管生成趋化因子CXCL3的转录水平和蛋白质水平也降低。我们首次在此报道了在PC-3细胞中靶向ESM-1,这导致细胞迁移减少,这可能至少部分与血管生成CXCL3趋化因子表达降低有关,在转染了ESM-1-siRNA的细胞中发现其表达减少。需要进一步的研究来确定ESM-1在前列腺癌细胞中的生物学作用以及与CXCL3表达的联系。