EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs.
EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs.
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DOI：
10.1155/2017/9653194
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Lim SK
中科院分区：
文献类型：
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作者：
Reiner AT;Tan S;Agreiter C;Auer K;Bachmayr-Heyda A;Aust S;Pecha N;Mandorfer M;Pils D;Brisson AR;Zeillinger R;Lim SK
高级别浆液性卵巢癌（HGSOC）是最具侵袭性的卵巢癌类型，是妇科癌症引起的大多数死亡的原因。在过去的几十年里，许多候选生物标志物被确定为这种疾病，但大多数都不够敏感或特异性的临床应用。因此，迫切需要HGSOC的新生物标志物。本研究的目的是通过从卵巢癌患者腹水中分离不同的细胞外囊泡（EV）类型，根据其对脂质结合蛋白的亲和力，并分析其蛋白质货物，以确定新的标志物。这种方法避免了使用生物流体进行生物标志物发现时的低信噪比和大的非EV复合物的污染问题。我们从卵巢癌或肝硬化患者的腹水中分离并分析了三种不同的EV群体，观察到与门脉高压性腹水相比，膜联蛋白V结合的EV在恶性腹水中具有更高水平的基质金属蛋白酶9。由于在其他EV群体中未检测到这种蛋白质，因此本研究验证了我们使用不同EV类型进行最佳生物标志物发现的方法。此外，膜联蛋白V结合EV中的MMP 9可能是具有增强的特异性的HGSOC生物标志物，因为其鉴定需要检测两种不同的组分，即脂质和蛋白质。
High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo. This approach circumvents the low signal-to-noise ratio when using biological fluids for biomarker discovery and the issue of contamination by large non-EV complexes. We isolated and analyzed three distinct EV populations from the ascites of patients with ovarian cancer or cirrhosis and observed that Annexin V-binding EVs have higher levels of matrix metalloproteinase 9 in malignant compared to portal-hypertensive ascites. As this protein was not detected in other EV populations, this study validates our approach of using different EV types for optimal biomarker discovery. Furthermore, MMP9 in Annexin V-binding EVs could be a HGSOC biomarker with enhanced specificity, because its identification requires detection of two distinct components, that is, lipid and protein.