MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma

BMC Cancer

Maria Eldh³  Roger Olofsson Bagge²  Cecilia Lässer³  Joar Svanvik¹  Margareta Sjöstrand³  Jan Mattsson²  Per Lindnér¹  Dong-Sic Choi⁴  Yong Song Gho⁴  Jan Lötvall³ 

[1] Transplant Institute, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden

[2] Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden

[3] Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

[4] Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology (POSTECH), Pohang, South Korea

关键词: Liver perfusion;    Uveal melanoma;    microRNA;    Biomarker;    Extracellular vesicles;    Exosomes;   

Others  :  1117869
DOI  :  10.1186/1471-2407-14-962

 received in 2014-05-06, accepted in 2014-12-10,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Eldh et al.; licensee BioMed Central.

【 图 表 】

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