title: MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Maria
authors.initials: M
authors.lastname: Eldh
authors.forename: Roger
authors.initials: R
authors.lastname: Olofsson Bagge
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lässer
authors.affiliation: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. joar.svanvik@liu.se.
authors.forename: Joar
authors.initials: J
authors.lastname: Svanvik
authors.forename: Margareta
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: Jan
authors.initials: J
authors.lastname: Mattsson
authors.forename: Per
authors.initials: P
authors.lastname: Lindnér
authors.forename: Dong-Sic
authors.initials: DS
authors.lastname: Choi
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
mesh_terms: D016022:Case-Control Studies; D045744:Cell Line, Tumor; D010478:Chemotherapy, Cancer, Regional Perfusion; D016000:Cluster Analysis; D055354:Exosomes / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000175:diagnosis / Q000556:secondary* / Q000628:therapy; D008279:Magnetic Resonance Imaging; D008545:Melanoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D035683:MicroRNAs / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D000098943:Uveal Melanoma
chemical_list: D035683:MicroRNAs