Eldh Maria, Olofsson Bagge Roger, Lässer Cecilia, Svanvik Joar, Sjöstrand Margareta, Mattsson Jan, Lindnér Per, Choi Dong-Sic, Gho Yong Song, Lötvall Jan
Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
BMC Cancer. 2014 Dec 16;14:962. doi: 10.1186/1471-2407-14-962.
Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.
Exosomes were isolated from the liver perfusate of twelve patients with liver metastases from uveal melanoma undergoing IHP. Exosomes were visualised by electron microscopy, and characterised by flow cytometry, Western blot and real-time PCR. Furthermore, the concentration of peripheral blood exosomes were measured and compared to healthy controls.
The liver perfusate contained Melan-A positive and RNA containing exosomes, with similar miRNA profiles among patients, but dissimilar miRNA compared to exosomes isolated from tumor cell cultures. Patients with metastatic uveal melanoma had a higher concentration of exosomes in their peripheral venous blood compared to healthy controls.
Melanoma exosomes are released into the liver circulation in metastatic uveal melanoma, and is associated with higher concentrations of exosomes in the systemic circulation. The exosomes isolated directly from liver circulation contain miRNA clusters that are different from exosomes from other cellular sources.
葡萄膜黑色素瘤是一种起源于眼部黑色素细胞的肿瘤，其中30%的患者会发生肝转移。外泌体是大多数细胞（包括恶性黑色素瘤细胞）释放的含小RNA的纳米囊泡。这项临床转化研究纳入了因转移性葡萄膜黑色素瘤接受孤立肝灌注（IHP）的患者，直接从肝灌注液中分离外泌体。目的是确定肝循环中是否存在外泌体，并确定这些外泌体是否可能源自黑色素瘤细胞。
从12例因葡萄膜黑色素瘤肝转移接受IHP的患者的肝灌注液中分离外泌体。通过电子显微镜观察外泌体，并通过流式细胞术、蛋白质免疫印迹和实时聚合酶链反应进行表征。此外，测量外周血外泌体的浓度并与健康对照进行比较。
肝灌注液中含有Melan-A阳性且含RNA的外泌体，患者之间的微小RNA（miRNA）谱相似，但与从肿瘤细胞培养物中分离的外泌体的miRNA不同。与健康对照相比，转移性葡萄膜黑色素瘤患者外周静脉血中的外泌体浓度更高。
在转移性葡萄膜黑色素瘤中，黑色素瘤外泌体释放到肝循环中，并与全身循环中外泌体浓度升高有关。直接从肝循环中分离的外泌体含有与其他细胞来源的外泌体不同的miRNA簇。
