Surface Proteomics of Cancer-Derived Extracellular Vesicles Reveals Universal Heat Shock Proteins and Cancer Signatures.

IF 6.3 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Leyla Ayse Erozenci, Fenna Feenstra, Sander R Piersma, Thang V Pham, Jianing Liu, Joke Wortel, Jan R T van Weering, Natasja Fj Dits, Guido Jenster, R Jeroen A van Moorselaar, Irene V Bijnsdorp, Connie R Jimenez
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引用次数: 0

Abstract

Extracellular vesicles (EVs) secreted by cancer cells are a valuable source of noninvasive biomarkers, as they are released into biofluids and reflect the molecular makeup of their cells of origin. To enable direct capture and detection of cancer-derived EVs, detailed knowledge of their surface proteome is essential. Here, we combined mild enzymatic treatment with mass spectrometry to analyze outward-facing proteins of EVs across a panel of 18 cell lines. This approach identified 1094 EV-associated surface proteins, including 144 transmembrane proteins involved in cellular communication and transport. Peptide-level analyses revealed that nearly 50% of multi-pass transmembrane proteins, such as ATP1A1, displayed their intracellular domains on the external EV surface. Out of a core set of 112 EV surface proteins shared across all cancer types, we report a top list of 15 highly abundant EV-surface proteins including ATP1A1, heat shock proteins (HSP)A8 and HSP90AB1 and nuclear proteins linked to EV biogenesis and cancer progression. This comprehensive profiling of EV surface proteomes from diverse cancer types reveals a robust set of pan-cancer EV surface markers with potential for diagnostic analysis.

癌症来源的细胞外囊泡的表面蛋白质组学揭示了普遍的热休克蛋白和癌症特征。
癌细胞分泌的细胞外囊泡(ev)是一种有价值的非侵入性生物标志物,因为它们被释放到生物体液中,反映了它们起源细胞的分子组成。为了能够直接捕获和检测癌症衍生的ev,对其表面蛋白质组的详细了解是必不可少的。在这里,我们将温和的酶处理与质谱相结合,分析了18个细胞系中ev的外向蛋白。该方法鉴定了1094种ev相关的表面蛋白,包括144种参与细胞通讯和运输的跨膜蛋白。肽水平分析显示,近50%的多通道跨膜蛋白,如ATP1A1,在外EV表面显示其胞内结构域。在所有癌症类型共有的112种EV表面蛋白的核心集合中,我们报告了15种高度丰富的EV表面蛋白的列表,包括ATP1A1,热休克蛋白HSPA8和HSP90AB1以及与EV生物发生和癌症进展相关的核蛋白。这种对不同癌症类型的EV表面蛋白质组的综合分析揭示了一组具有诊断分析潜力的泛癌症EV表面标记。意义:在过去的十年中,电动汽车已经成为生理和病理背景下细胞间通讯的重要介质。虽然人们对EV蛋白质组已经很熟悉,但对于哪些蛋白质在EV表面是向外的,还缺乏详细的知识,这将使开发分离癌症特异性EV的工具成为可能。我们报道了多种癌症类型的EV表面蛋白质组,揭示了普遍存在的表面蛋白和肿瘤类型特异性标记。15种泛癌EV表面蛋白中,热休克蛋白HSPA8、HSP90AB1和ATP1A1位居前列。这些发现不仅促进了我们对EV表面分子结构的理解,而且为开发针对不同癌症的诊断和治疗应用的靶向EV捕获策略奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular & Cellular Proteomics
Molecular & Cellular Proteomics 生物-生化研究方法
CiteScore
11.50
自引率
4.30%
发文量
131
审稿时长
84 days
期刊介绍: The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes
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