Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes
Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes
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DOI：
10.1016/j.canlet.2008.12.028
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发表时间：
2009-06-08
期刊：
影响因子：
9.7
通讯作者：
Altevogt, Peter
中科院分区：
文献类型：
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作者：
Keller, Sascha;Konig, Anne-Kathleen;Altevogt, Peter
外体是从许多不同类型的细胞中释放出来的膜小泡。肿瘤来源的外切体在免疫抑制中发挥作用。我们推测，在卵巢癌患者中，最初在局部腹部产生的外切体可能成为全身性的。我们对卵巢癌患者的腹水和血液样本进行了检查，以确定外切体的存在。我们还研究了免疫细胞对胞外体摄取的要求，磷脂酰丝氨酸(PS)作为摄取信号的作用，以及外切体应用对肿瘤生长的影响。我们使用卵巢癌细胞系的外切体、恶性腹水和卵巢癌患者的血清，通过超速离心法分离。通过Anexin-V-FITC对吸附在外切体上的乳胶珠进行染色，检测PS-由外切体显示。对于摄取实验，标记的外切体在存在或不存在冷Annexin-V竞争对手的情况下暴露于细胞中。荧光显微镜和细胞荧光分析检测摄取情况。以CD1nu/nu小鼠卵巢癌细胞SKOV3ip为模型，研究了外切体对肿瘤生长的影响。我们发现恶性腹水来源的外体携带肿瘤进展相关蛋白，如L1CAM、CD24、ADAM10和EMMPRIN。我们观察到，外体通过血流变得系统化。NK细胞摄取卵巢癌外切体需要PS的存在，但PS的存在是不够的。将恶性腹水来源的外切体应用于荷瘤小鼠，可促进肿瘤生长。仅从一毫升血液中就能分离出肿瘤患者血清中的外切体，这种分析可以用于诊断目的。我们认为肿瘤来源的外切体可能在肿瘤进展中发挥作用。(C)2009爱思唯尔爱尔兰有限公司。保留所有权利。
Exosomes are membrane vesicles that are released from many different cell types. Tumor derived-exosomes play a role in immune suppression. We hypothesized that in ovarian carcinoma patients exosomes initially produced at the local abdominal site may become systemic. We examined paired samples of ascites and blood from ovarian carcinoma patients for the presence of exosomes. We also studied the requirements for exosomal uptake by immune cells, the role of phosphatidyl-serine (PS) as uptake signal and the effect of exosome application on tumor growth. We used exosomes from ovarian carcinoma cell lines, malignant ascites and sera from ovarian carcinoma patients isolated by ultracentrifugation. PS-displayed by exosomes was detected by Anexin-V-FITC staining of latex beads adsorbed exosomes. For uptake experiments, labeled exosomes were exposed to cells in the presence or absence of cold Annexin-V as competitor. Uptake was examined by fluorescent microscopy and cytofluorographic analysis. Effects of exosomes on tumor growth were studied using SKOV3ip ovarian carcinoma cells in CD1 nu/nu mice. We found that malignant ascites-derived exosomes cargo tumor progression related proteins such as L1CAM, CD24, ADAM10, and EMMPRIN. We observed that exosomes become systemic via the blood stream. Uptake of ovarian carcinoma exosomes by NK cells was found to require PS at the exosomal surface but the presence of PS was not sufficient. Application of malignant ascites-derived exosomes to tumor-bearing mice resulted in augmented tumor growth. Exosomes from the serum of tumor patients could be isolated from only one ml of blood and this analysis could serve for diagnostic purposes. We propose that tumor-derived exosomes could play a role in tumor progression. (c) 2009 Elsevier Ireland Ltd. All rights reserved.