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高级卵巢癌中小细胞外囊泡表面的金属蛋白酶:与腹水体积和腹膜癌指数的关系。

Metalloproteinases at the surface of small extrcellular vesicles in advanced ovarian cancer: Relationships with ascites volume and peritoneal canceromatosis index.

机构信息

Cancer Research Institute, Тomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia; Siberian State Medical University, Tomsk, Russia.

Cancer Research Institute, Тomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia.

出版信息

Clin Chim Acta. 2019 Jul;494:116-122. doi: 10.1016/j.cca.2019.03.1621. Epub 2019 Mar 20.

Abstract

Metalloproteinases and their extracellular matrix metalloproteinase inducer (EMMPRIN) play an essential role in the regulation of signaling from growth factors receptors and adhesion molecules, cell motility and extracellular matrix degradation. The aim of the study was to evaluate the relationship between the levels of small extracellular vesicles (sEVs) metalloproteinases, such as ADAM10, ADAM17, MMP2, MMP9 and EMMPRIN and ascites volume and peritoneal canceromatosis index in advanced ovarian cancer patients (OCPs). The subpopulations of metalloproteinases at the surface of sEVs of borderline ovarian tumor patients (BOTPs) (n = 20, 36.5 ± 2.5 years) and previously untreated advanced OCPs (n = 35, 56.5 ± 2.5 years) were evaluated using flow cytometry. The metalloproteinase subpopulations of CD9-positive sEVs isolated from plasma of BOTPs and OCPs appeared to be quite similar. However, a significant difference in the expression of ADAM-metalloproteinases in ascites sEVs was found between BOTPs and OCPs. The level of sEVs metalloproteinases in OCPs significantly depended on the ascites volume. A statistically significant relationship between the level of ADAM10+/ADAM17- subpopulation in plasma sEVs and the peritoneal canceromatosis index was found (R = 0.66, p < .05). The levels of metalloproteinases and EMMPRIN in circulating sEVs, as well as the assessment of individual subpopulations may be promising approaches to OCPs managing.

摘要

金属蛋白酶及其细胞外基质金属蛋白酶诱导因子 (EMMPRIN) 在调节生长因子受体和黏附分子信号转导、细胞迁移和细胞外基质降解中发挥着重要作用。本研究旨在评估晚期卵巢癌患者(OCPs)中小细胞外囊泡(sEVs)金属蛋白酶(如 ADAM10、ADAM17、MMP2、MMP9 和 EMMPRIN)水平与腹水体积和腹膜癌转移指数之间的关系。采用流式细胞术评估了边界性卵巢肿瘤患者(BOTPs)(n=20,36.5±2.5 岁)和未经治疗的晚期 OCPs(n=35,56.5±2.5 岁)sEV 表面金属蛋白酶亚群。BOTPs 和 OCPs 血浆中 CD9 阳性 sEV 分离的金属蛋白酶亚群似乎非常相似,但在 BOTPs 和 OCPs 的腹水 sEV 中发现 ADAM-金属蛋白酶的表达存在显著差异。OCPs 的 sEV 金属蛋白酶水平与腹水体积显著相关。还发现血浆 sEV 中 ADAM10+/ADAM17-亚群水平与腹膜癌转移指数之间存在统计学显著关系(R=0.66,p<0.05)。循环 sEVs 中金属蛋白酶和 EMMPRIN 的水平以及对个体亚群的评估可能是 OCPs 管理的有前途的方法。

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