Jang Su Chul, Crescitelli Rossella, Cvjetkovic Aleksander, Belgrano Valerio, Olofsson Bagge Roger, Sundfeldt Karin, Ochiya Takahiro, Kalluri Raghu, Lötvall Jan
Krefting Research Center, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Department of Surgery and Sahlgrenska Cancer Center, Institute of Clinical Sciences, the Sahgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
J Extracell Vesicles. 2019 Aug 27;8(1):1635420. doi: 10.1080/20013078.2019.1635420. eCollection 2019.
Extracellular vesicles (EVs), including exosomes and microvesicles, are secreted from all cells, and convey messages between cells in health and disease. However, the diversity of EV subpopulations is only beginning to be explored. Since EVs have been implicated in tumour microenvironmental communication, we started to determine the diversity of EVs specifically in this tissue. To do this, we isolated EVs directly from patient melanoma metastatic tissues. Using EV membrane isolation and mass spectrometry analysis, we discovered enrichment of mitochondrial membrane proteins in the melanoma tissue-derived EVs, compared to non-melanoma-derived EVs. Interestingly, two mitochondrial inner membrane proteins MT-CO2 (encoded by the mitochondrial genome) and COX6c (encoded by the nuclear genome) were highly prevalent in the plasma of melanoma patients, as well as in ovarian and breast cancer patients. Furthermore, this subpopulation of EVs contains active mitochondrial enzymes. In summary, tumour tissues are enriched in EVs with mitochondrial membrane proteins and these mitochondrial membrane proteins can be detected in plasma and are increased in melanoma, ovarian cancer as well as breast cancer.
细胞外囊泡（EVs），包括外泌体和微囊泡，由所有细胞分泌，并在健康和疾病状态下的细胞间传递信息。然而，EV亚群的多样性才刚刚开始被探索。由于EVs与肿瘤微环境通讯有关，我们开始确定EVs在该组织中的特异性多样性。为此，我们直接从患者黑色素瘤转移组织中分离出EVs。通过EV膜分离和质谱分析，我们发现与非黑色素瘤来源的EVs相比，黑色素瘤组织来源的EVs中线粒体膜蛋白富集。有趣的是，两种线粒体内膜蛋白MT-CO2（由线粒体基因组编码）和COX6c（由核基因组编码）在黑色素瘤患者的血浆中以及卵巢癌和乳腺癌患者的血浆中高度普遍。此外，这一EV亚群含有活性线粒体酶。总之，肿瘤组织中富含带有线粒体膜蛋白的EVs，这些线粒体膜蛋白可在血浆中检测到，并且在黑色素瘤、卵巢癌和乳腺癌中含量增加。
