Skip to main content
Top
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

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

Authors: Maria Eldh, Roger Olofsson Bagge, Cecilia Lässer, Joar Svanvik, Margareta Sjöstrand, Jan Mattsson, Per Lindnér, Dong-Sic Choi, Yong Song Gho, Jan Lötvall

Published in: BMC Cancer | Issue 1/2014

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Harding C, Heuser J, Stahl P: Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983, 97: 329-339. 10.1083/jcb.97.2.329.CrossRefPubMed Harding C, Heuser J, Stahl P: Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983, 97: 329-339. 10.1083/jcb.97.2.329.CrossRefPubMed
2.
go back to reference Pan B-T, Johnstone RM: Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell. 1983, 33: 967-978. 10.1016/0092-8674(83)90040-5.CrossRefPubMed Pan B-T, Johnstone RM: Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell. 1983, 33: 967-978. 10.1016/0092-8674(83)90040-5.CrossRefPubMed
3.
go back to reference Pan BT, Teng K, Wu C, Adam M, Johnstone RM: Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol. 1985, 101: 942-948. 10.1083/jcb.101.3.942.CrossRefPubMed Pan BT, Teng K, Wu C, Adam M, Johnstone RM: Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol. 1985, 101: 942-948. 10.1083/jcb.101.3.942.CrossRefPubMed
4.
go back to reference Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C: Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987, 262: 9412-9420.PubMed Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C: Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987, 262: 9412-9420.PubMed
5.
go back to reference Thery C, Zitvogel L, Amigorena S: Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002, 2: 569-579.PubMed Thery C, Zitvogel L, Amigorena S: Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002, 2: 569-579.PubMed
6.
go back to reference Van Niel G, Raposo G, Candalh C, Boussac M, Hershberg R, Cerf-Bensussan N, Heyman M: Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology. 2001, 121: 337-349. 10.1053/gast.2001.26263.CrossRefPubMed Van Niel G, Raposo G, Candalh C, Boussac M, Hershberg R, Cerf-Bensussan N, Heyman M: Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology. 2001, 121: 337-349. 10.1053/gast.2001.26263.CrossRefPubMed
7.
go back to reference Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ: B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996, 183: 1161-1172. 10.1084/jem.183.3.1161.CrossRefPubMed Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ: B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996, 183: 1161-1172. 10.1084/jem.183.3.1161.CrossRefPubMed
8.
go back to reference Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S: Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999, 147: 599-610. 10.1083/jcb.147.3.599.CrossRefPubMedPubMedCentral Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S: Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999, 147: 599-610. 10.1083/jcb.147.3.599.CrossRefPubMedPubMedCentral
9.
go back to reference Blanchard N, Lankar D, Faure F, Regnault A, Dumont C, Raposo G, Hivroz C: TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/{zeta} complex. J Immunol. 2002, 168: 3235-3241. 10.4049/jimmunol.168.7.3235.CrossRefPubMed Blanchard N, Lankar D, Faure F, Regnault A, Dumont C, Raposo G, Hivroz C: TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/{zeta} complex. J Immunol. 2002, 168: 3235-3241. 10.4049/jimmunol.168.7.3235.CrossRefPubMed
10.
go back to reference Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L, et al: Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001, 7: 297-303. 10.1038/85438.CrossRefPubMed Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L, et al: Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001, 7: 297-303. 10.1038/85438.CrossRefPubMed
11.
go back to reference Andre F, Schartz NEC, Movassagh M, Flament C, Pautier P, Morice P, Pomel C, Lhomme C, Escudier B, Le Chevalier T, Tursz T, Amigorena S, Raposo G, Angevin E, Zitvogel L: Malignant effusions and immunogenic tumour-derived exosomes. The Lancet. 2002, 360: 295-305. 10.1016/S0140-6736(02)09552-1.CrossRef Andre F, Schartz NEC, Movassagh M, Flament C, Pautier P, Morice P, Pomel C, Lhomme C, Escudier B, Le Chevalier T, Tursz T, Amigorena S, Raposo G, Angevin E, Zitvogel L: Malignant effusions and immunogenic tumour-derived exosomes. The Lancet. 2002, 360: 295-305. 10.1016/S0140-6736(02)09552-1.CrossRef
12.
go back to reference Caby M-P, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C: Exosomal-like vesicles are present in human blood plasma. Int Immunol. 2005, 17: 879-887. 10.1093/intimm/dxh267.CrossRefPubMed Caby M-P, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C: Exosomal-like vesicles are present in human blood plasma. Int Immunol. 2005, 17: 879-887. 10.1093/intimm/dxh267.CrossRefPubMed
13.
go back to reference Pisitkun T, Shen R-F, Knepper MA: Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004, 101: 13368-13373. 10.1073/pnas.0403453101.CrossRefPubMedPubMedCentral Pisitkun T, Shen R-F, Knepper MA: Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004, 101: 13368-13373. 10.1073/pnas.0403453101.CrossRefPubMedPubMedCentral
14.
go back to reference Admyre C, Johansson SM, Qazi KR, Filen J-J, Lahesmaa R, Norman M, Neve EPA, Scheynius A, Gabrielsson S: Exosomes with immune modulatory features Are present in human breast milk. J Immunol. 2007, 179: 1969-1978. 10.4049/jimmunol.179.3.1969.CrossRefPubMed Admyre C, Johansson SM, Qazi KR, Filen J-J, Lahesmaa R, Norman M, Neve EPA, Scheynius A, Gabrielsson S: Exosomes with immune modulatory features Are present in human breast milk. J Immunol. 2007, 179: 1969-1978. 10.4049/jimmunol.179.3.1969.CrossRefPubMed
15.
go back to reference Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007, 9: 654-659. 10.1038/ncb1596.CrossRefPubMed Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007, 9: 654-659. 10.1038/ncb1596.CrossRefPubMed
16.
go back to reference Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, Ratajczak MZ: Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 2006, 20: 847-856. 10.1038/sj.leu.2404132.CrossRefPubMed Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, Ratajczak MZ: Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 2006, 20: 847-856. 10.1038/sj.leu.2404132.CrossRefPubMed
17.
go back to reference Aliotta JM, Pereira M, Johnson KW, de Paz N, Dooner MS, Puente N, Ayala C, Brilliant K, Berz D, Lee D, Ramratnam B, McMillan PN, Hixson DC, Josic D, Quesenberry PJ: Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription. Exp Hematol. 2010, 38: 233-245. 10.1016/j.exphem.2010.01.002.CrossRefPubMedPubMedCentral Aliotta JM, Pereira M, Johnson KW, de Paz N, Dooner MS, Puente N, Ayala C, Brilliant K, Berz D, Lee D, Ramratnam B, McMillan PN, Hixson DC, Josic D, Quesenberry PJ: Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription. Exp Hematol. 2010, 38: 233-245. 10.1016/j.exphem.2010.01.002.CrossRefPubMedPubMedCentral
18.
go back to reference Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Carter BS, Krichevsky AM, Breakefield XO: Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008, 10: 1470-1476. 10.1038/ncb1800.CrossRefPubMedPubMedCentral Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Carter BS, Krichevsky AM, Breakefield XO: Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008, 10: 1470-1476. 10.1038/ncb1800.CrossRefPubMedPubMedCentral
19.
go back to reference Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH: Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer. 2009, 10: 42-46. 10.3816/CLC.2009.n.006.CrossRefPubMed Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH: Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer. 2009, 10: 42-46. 10.3816/CLC.2009.n.006.CrossRefPubMed
21.
go back to reference Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5.CrossRefPubMed Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5.CrossRefPubMed
24.
go back to reference Mattick JS, Makunin IV: Small regulatory RNAs in mammals. Hum Mol Genet. 2005, 14 Spec No 1: R121-R132.CrossRefPubMed Mattick JS, Makunin IV: Small regulatory RNAs in mammals. Hum Mol Genet. 2005, 14 Spec No 1: R121-R132.CrossRefPubMed
25.
go back to reference Hurst EA, Harbour JW, Cornelius LA: Ocular melanoma: a review and the relationship to cutaneous melanoma. Arch Dermatol. 2003, 139: 1067-1073. 10.1001/archderm.139.8.1067.CrossRefPubMed Hurst EA, Harbour JW, Cornelius LA: Ocular melanoma: a review and the relationship to cutaneous melanoma. Arch Dermatol. 2003, 139: 1067-1073. 10.1001/archderm.139.8.1067.CrossRefPubMed
26.
go back to reference Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Hawkins BS, Hayman JA, Jaiyesimi I, Jampol LM, Kirkwood JM, Koh WJ, Robertson DM, Shaw JM, Straatsma BR, Thoma J, Collaborative Ocular Melanoma Study G: Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005, 123: 1639-1643.CrossRefPubMed Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Hawkins BS, Hayman JA, Jaiyesimi I, Jampol LM, Kirkwood JM, Koh WJ, Robertson DM, Shaw JM, Straatsma BR, Thoma J, Collaborative Ocular Melanoma Study G: Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005, 123: 1639-1643.CrossRefPubMed
27.
go back to reference Mariani P, Piperno-Neumann S, Servois V, Berry MG, Dorval T, Plancher C, Couturier J, Levy-Gabriel C, Lumbroso-Le Rouic L, Desjardins L, Salmon RJ: Surgical management of liver metastases from uveal melanoma: 16 years’ experience at the Institut Curie. Eur J Surg Oncol. 2009, 35: 1192-1197. 10.1016/j.ejso.2009.02.016.CrossRefPubMed Mariani P, Piperno-Neumann S, Servois V, Berry MG, Dorval T, Plancher C, Couturier J, Levy-Gabriel C, Lumbroso-Le Rouic L, Desjardins L, Salmon RJ: Surgical management of liver metastases from uveal melanoma: 16 years’ experience at the Institut Curie. Eur J Surg Oncol. 2009, 35: 1192-1197. 10.1016/j.ejso.2009.02.016.CrossRefPubMed
28.
go back to reference Sharma KV, Gould JE, Harbour JW, Linette GP, Pilgram TK, Dayani PN, Brown DB: Hepatic arterial chemoembolization for management of metastatic melanoma. AJR Am J Roentgenol. 2008, 190: 99-104. 10.2214/AJR.07.2675.CrossRefPubMed Sharma KV, Gould JE, Harbour JW, Linette GP, Pilgram TK, Dayani PN, Brown DB: Hepatic arterial chemoembolization for management of metastatic melanoma. AJR Am J Roentgenol. 2008, 190: 99-104. 10.2214/AJR.07.2675.CrossRefPubMed
29.
go back to reference Rizell M, Mattson J, Cahlin C, Hafstrom L, Lindner P, Olausson M: Isolated hepatic perfusion for liver metastases of malignant melanoma. Melanoma Res. 2008, 18: 120-126. 10.1097/CMR.0b013e3282f8e3c9.CrossRefPubMed Rizell M, Mattson J, Cahlin C, Hafstrom L, Lindner P, Olausson M: Isolated hepatic perfusion for liver metastases of malignant melanoma. Melanoma Res. 2008, 18: 120-126. 10.1097/CMR.0b013e3282f8e3c9.CrossRefPubMed
30.
go back to reference Lässer C, Eldh M, Lötvall J: Isolation and characterization of RNA-containing exosomes. J Vis Exp. 2012, 2012: e3037- Lässer C, Eldh M, Lötvall J: Isolation and characterization of RNA-containing exosomes. J Vis Exp. 2012, 2012: e3037-
31.
go back to reference de Hoon MJ, Imoto S, Nolan J, Miyano S: Open source clustering software. Bioinformatics. 2004, 20: 1453-1454. 10.1093/bioinformatics/bth078.CrossRefPubMed de Hoon MJ, Imoto S, Nolan J, Miyano S: Open source clustering software. Bioinformatics. 2004, 20: 1453-1454. 10.1093/bioinformatics/bth078.CrossRefPubMed
32.
go back to reference Vlachos IS, Kostoulas N, Vergoulis T, Georgakilas G, Reczko M, Maragkakis M, Paraskevopoulou MD, Prionidis K, Dalamagas T, Hatzigeorgiou AG: DIANA miRPath v. 2.0: investigating the combinatorial effect of microRNAs in pathways. Nucleic Acids Res. 2012, 40: W498-W504. 10.1093/nar/gks494.CrossRefPubMedPubMedCentral Vlachos IS, Kostoulas N, Vergoulis T, Georgakilas G, Reczko M, Maragkakis M, Paraskevopoulou MD, Prionidis K, Dalamagas T, Hatzigeorgiou AG: DIANA miRPath v. 2.0: investigating the combinatorial effect of microRNAs in pathways. Nucleic Acids Res. 2012, 40: W498-W504. 10.1093/nar/gks494.CrossRefPubMedPubMedCentral
33.
go back to reference Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000, 92: 205-216. 10.1093/jnci/92.3.205.CrossRefPubMed Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000, 92: 205-216. 10.1093/jnci/92.3.205.CrossRefPubMed
34.
go back to reference Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D: Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012, 18: 883-891. 10.1038/nm.2753.CrossRefPubMedPubMedCentral Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D: Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012, 18: 883-891. 10.1038/nm.2753.CrossRefPubMedPubMedCentral
35.
go back to reference Hood JL, San RS, Wickline SA: Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 2011, 71: 3792-3801. 10.1158/0008-5472.CAN-10-4455.CrossRefPubMed Hood JL, San RS, Wickline SA: Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 2011, 71: 3792-3801. 10.1158/0008-5472.CAN-10-4455.CrossRefPubMed
36.
go back to reference Jung T, Castellana D, Klingbeil P, Cuesta Hernandez I, Vitacolonna M, Orlicky DJ, Roffler SR, Brodt P, Zoller M: CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia. 2009, 11: 1093-1105.CrossRefPubMedPubMedCentral Jung T, Castellana D, Klingbeil P, Cuesta Hernandez I, Vitacolonna M, Orlicky DJ, Roffler SR, Brodt P, Zoller M: CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia. 2009, 11: 1093-1105.CrossRefPubMedPubMedCentral
37.
go back to reference Ostenfeld MS, Jeppesen DK, Laurberg JR, Boysen AT, Bramsen JB, Primdal-Bengtson B, Hendrix A, Lamy P, Dagnaes-Hansen F, Rasmussen MH, Bui KH, Fristrup N, Christensen EI, Nordentoft I, Morth JP, Jensen JB, Pedersen JS, Beck M, Theodorescu D, Borre M, Howard KA, Dyrskjot L, Orntoft TF: Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer Res. 2014, 74: 5758-5771. 10.1158/0008-5472.CAN-13-3512.CrossRefPubMed Ostenfeld MS, Jeppesen DK, Laurberg JR, Boysen AT, Bramsen JB, Primdal-Bengtson B, Hendrix A, Lamy P, Dagnaes-Hansen F, Rasmussen MH, Bui KH, Fristrup N, Christensen EI, Nordentoft I, Morth JP, Jensen JB, Pedersen JS, Beck M, Theodorescu D, Borre M, Howard KA, Dyrskjot L, Orntoft TF: Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer Res. 2014, 74: 5758-5771. 10.1158/0008-5472.CAN-13-3512.CrossRefPubMed
38.
go back to reference Yan D, Dong XD, Chen X, Yao S, Wang L, Wang J, Wang C, Hu DN, Qu J, Tu L: Role of microRNA-182 in posterior uveal melanoma: regulation of tumor development through MITF, BCL2 and cyclin D2. PLoS One. 2012, 7: e40967-10.1371/journal.pone.0040967.CrossRefPubMedPubMedCentral Yan D, Dong XD, Chen X, Yao S, Wang L, Wang J, Wang C, Hu DN, Qu J, Tu L: Role of microRNA-182 in posterior uveal melanoma: regulation of tumor development through MITF, BCL2 and cyclin D2. PLoS One. 2012, 7: e40967-10.1371/journal.pone.0040967.CrossRefPubMedPubMedCentral
39.
go back to reference Yan D, Zhou X, Chen X, Hu DN, Dong XD, Wang J, Lu F, Tu L, Qu J: MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci. 2009, 50: 1559-1565.CrossRefPubMed Yan D, Zhou X, Chen X, Hu DN, Dong XD, Wang J, Lu F, Tu L, Qu J: MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci. 2009, 50: 1559-1565.CrossRefPubMed
40.
go back to reference Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, Lopes B, Schiff D, Purow B, Abounader R: MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 2009, 69: 7569-7576. 10.1158/0008-5472.CAN-09-0529.CrossRefPubMedPubMedCentral Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, Lopes B, Schiff D, Purow B, Abounader R: MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 2009, 69: 7569-7576. 10.1158/0008-5472.CAN-09-0529.CrossRefPubMedPubMedCentral
41.
go back to reference Yang C, Wei W: The miRNA expression profile of the uveal melanoma. Science China Life sciences. 2011, 54: 351-358. 10.1007/s11427-011-4149-y.CrossRefPubMed Yang C, Wei W: The miRNA expression profile of the uveal melanoma. Science China Life sciences. 2011, 54: 351-358. 10.1007/s11427-011-4149-y.CrossRefPubMed
Metadata
Title
MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma
Authors
Maria Eldh
Roger Olofsson Bagge
Cecilia Lässer
Joar Svanvik
Margareta Sjöstrand
Jan Mattsson
Per Lindnér
Dong-Sic Choi
Yong Song Gho
Jan Lötvall
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-962

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine