Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane QLD 4029, Australia.
Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
Clin Sci (Lond). 2018 Sep 18;132(18):2029-2044. doi: 10.1042/CS20180425. Print 2018 Sep 28.
Ovarian cancer has resulted in over 140 000 deaths reported annually worldwide. This is often attributed to cellular changes in the microenvironment, including increased migration of mesenchymal stem cells (MSCs) and endothelial cells (ECs) to facilitate metastasis. Recently, the ability of exosomes to communicate signals between cells (and promote cancer progression) has been established. In the present study, we explored the effect of exosomes on cells present in the tumour microenvironment. Exosomes were isolated from ovarian cancer cells with different invasive capacity (high = SKOV-3 and low = OVCAR-3) by differential and buoyant density centrifugation and characterised using nanoparticle tracking analysis (NTA), Western blot, and EM. Exosome secretion was positively correlated with invasiveness of releasing cells. Proteomic analyses identified common and unique proteins between exosomes from SKOV-3 and OVCAR-3 with gene ontology analyses revealing that these exosomes are involved in the regulation of cell migration. Since the tumour microenvironment contains multiple cell types, including MSCs and ECs, we examined the effect of these exosomes on MSC and EC migration. Exosomes promoted MSC and EC migration in a time- and concentration-dependent manner. The effect of exosomes isolated from SKOV-3 on cell migration was significantly higher compared with exosomes from OVCAR-3. Thus, we suggest that exosomes from ovarian cancer cells contain a specific set of proteins that are representative of its cell of origin and the invasive capacity.
卵巢癌每年导致全球超过 14 万人死亡。这通常归因于微环境中的细胞变化，包括间充质干细胞（MSCs）和内皮细胞（ECs）的迁移增加，以促进转移。最近，外泌体在细胞间传递信号（并促进癌症进展）的能力已经得到证实。在本研究中，我们探讨了外泌体对肿瘤微环境中细胞的影响。通过差速和浮力密度离心从具有不同侵袭能力（高 = SKOV-3 和低 = OVCAR-3）的卵巢癌细胞中分离出外泌体，并通过纳米颗粒跟踪分析（NTA）、Western blot 和 EM 进行表征。外泌体的分泌与释放细胞的侵袭性呈正相关。蛋白质组学分析鉴定了 SKOV-3 和 OVCAR-3 来源的外泌体之间的共同和独特蛋白，基因本体论分析表明这些外泌体参与细胞迁移的调节。由于肿瘤微环境包含多种细胞类型，包括 MSCs 和 ECs，我们研究了这些外泌体对 MSC 和 EC 迁移的影响。外泌体以时间和浓度依赖的方式促进 MSC 和 EC 的迁移。与 OVCAR-3 来源的外泌体相比，来自 SKOV-3 的外泌体对细胞迁移的影响明显更高。因此，我们认为卵巢癌细胞来源的外泌体含有一组特定的蛋白质，代表其细胞起源和侵袭能力。
