Targeting Oncofoetal Chondroitin Sulphate Allows Identification of Tumour-Derived Extracellular Vesicles

IF 14.5 1区医学 Q1 CELL BIOLOGY

Journal of Extracellular Vesicles Pub Date : 2025-06-17 DOI:10.1002/jev2.70106

Agustin Enciso-Martinez, Caroline Løppke, Joyce J. Koene, Jade Ebbelaar, Meike van der Geest, Mandy Los, Emma P. E. M. Boerrigter, Robert Dagil, Tobias Gustavsson, Elena E. Vidal-Calvo, Ton G. van Leeuwen, Roman I. Koning, Nick van Es, Ali Salanti, Edwin van der Pol, Rienk Nieuwland, Mette Ø. Agerbæk, Peter ten Dijke

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Abstract

Tumour-derived extracellular vesicles (tdEVs) are widely studied for their contribution to tumour progression and metastasis. These studies are hampered by the lack of specific markers to identify the tdEVs. Here, we show that oncofoetal chondroitin sulphate, a malignancy-associated glycosaminoglycan modification, is present on tdEVs and can be targeted by the malaria VAR2CSA protein or C9 antibody. Using a fluorescently labelled recombinant VAR2CSA protein, we identified EVs from cancer cells in vitro by super-resolution fluorescence microscopy and flow cytometry, as well as in a proof-of-concept study using plasma samples from pancreatic adenocarcinoma patients. Thus, the binding of VAR2CSA offers a tool to identify tdEVs, and can be used to explore their function and biomarker potential in cancer.

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靶向肿瘤胎儿硫酸软骨素可识别肿瘤来源的细胞外囊泡

肿瘤源性细胞外囊泡（tdEVs）因其在肿瘤进展和转移中的作用而被广泛研究。由于缺乏识别tdev的特异性标记物，这些研究受到了阻碍。在这里，我们发现肿瘤胎儿硫酸软骨素（一种恶性肿瘤相关的糖胺聚糖修饰）存在于tdev上，并且可以被疟疾VAR2CSA蛋白或C9抗体靶向。使用荧光标记的重组VAR2CSA蛋白，我们通过超分辨率荧光显微镜和流式细胞术在体外癌细胞中鉴定出ev，并在一项使用胰腺腺癌患者血浆样本的概念验证研究中鉴定出ev。因此，结合VAR2CSA提供了一种鉴定tdev的工具，并可用于探索其在癌症中的功能和生物标志物潜力。

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来源期刊

Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

27.30

自引率

4.40%

发文量

115

审稿时长

12 weeks

期刊介绍： The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.