Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
J Extracell Vesicles. 2024 Mar;13(3):e12420. doi: 10.1002/jev2.12420.
High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV-associated proteins' but also defined their subset unique to HGSC ascites. Using single-cell RNA sequencing data, we mapped the origin of HGSC-specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non-malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type-specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics.
卵巢、输卵管和腹膜高级别浆液性癌（HGSC）是最常见的卵巢癌类型，属于最致命的恶性肿瘤之一。许多 HGSC 患者的腹膜中有过多的液体，称为腹水。腹水是一种含有各种细胞、蛋白质和细胞外囊泡（EVs）的肿瘤微环境（TME）。我们通过正交方法从患者的腹水中分离 EVs，并通过质谱进行分析。我们不仅鉴定了一组“核心腹水 EV 相关蛋白”，还定义了其 HGSC 腹水特有的亚组。使用单细胞 RNA 测序数据，我们将 HGSC 特异性 EV 的起源映射到腹水中存在的不同类型的细胞。令人惊讶的是，EV 并非主要来自肿瘤细胞，而是来自非恶性细胞类型，如巨噬细胞和成纤维细胞。结合对匹配样本中 EV 蛋白组成的分析，对腹水细胞进行流式细胞术表明，与分析腹水细胞相比，分析 HGSC 中细胞特异性 EV 标志物具有更大的预后潜力。总之，我们提供的证据表明，EV 的蛋白质组学分析可以定义 HGSC TME 的细胞组成。这一发现为更好地理解 EV 在肿瘤促进/预防中的作用以及改进 HGSC 诊断开辟了许多途径。
