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Aug 23, 2016

Join the SELECTBIO Extracellular Vesicles Virtual Event made available from September 21st, and hear leading researchers talk about topics within EV biology and therapeutic potential!

 

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General information, events and/or links.

 

 

Research production in RRNEV

Cooperative research projects in RRNEV, 2013 – 2015/2016

RRNEV has aimed to establish coordinated research projects between the project groups. These projects have been supported by funding from RRNEV. The fundings have been based on evaluation of the projects by all the network groups.

 

“Implementation and validation of methods for isolation of EVs from plasma”.

RRNEV groups involved: The Blood Cell Research Group, Thermo Fisher – Life Sciences Group, The OncoGenomics Group

Project leader: Kari Bente Foss Haug

Aims: To establish extended use of size exclusion chromatography (SEC) as a standardized preclearing step of plasma samples before EV-specific isolation and downstream characterization. As a part of the project, a bachelor thesis was recently conducted by biomedical laboratory scientist Tine Hiorth Schøyen; “Quantification of specific microRNAs in extracellular vesicles (EVs) from plasma”.

 

“Urinary extracellular vesicles as source of prostate cancer biomarkers”.

RRNEV groups involved: The Microvesicles and Prostate Cancer: Biomarkers and Release Mechanisms Group, The Blood Cell Research Group

Project leader: Alicia Llorente

Aims: To develop simple methods for the isolation of urinary extracellular vesicles (EVs) and to identify prostate cancer biomarkers in urinary EVs.

 

“Extracellular vesicles as potential biomarker of hypoxia-induced rectal cancer aggressiveness”.

RRNEV groups involved: The Clinical and Molecular in Rectal Cancer (CMOR) Group, The Microvesicles and Prostate Cancer: Biomarkers and Release Mechanisms Group, Thermo Fisher – Life Sciences Group

Project leader: Anne Hansen Ree

Aims: Colorectal cancers, like most solid cancers, contain hypoxic regions that are characterized by oxygen deprivation as a result of differential perfusion of oxygen. Hypoxia is an important hallmark of the tumor environment and a main mechanism both in resistance to therapy and metastatic progression. The overall aim of the project is to investigate extracellular vesicles as an attractive biomarker approach for characterizing the hypoxic phenotype.

 

“EV profiles of primary cell lines derived from Pancreatic Ductal Adenocarcinoma (PDAC) patients”.

RRNEV groups involved: The OncoGenomics Group, The Blood Cell Research Group

External collaborators: David Lyden, Bruno C. da Silva, Weill Medical College of Cornell University, USA, and I. Gladhaug, V. Tjomsland, E. Munthe, OUH

Project leader: Elin Kure

Aims: The overall goal is to evaluate EV profiles of miRNAs as diagnostic and/or prognostic biomarkers in plasma of pancreatic cancer patients as well as in serum of lung cancer patients. The method, when established, will also be used to identify miRNAs in EVs in serum of breast cancer patients.

 

“Functional microvesicle (MV)-associated tissue factor (TF) activity as a potential biomarker of thrombosis in cancer”.

 

RRNEV groups involved: The Blood Cell Research Group, The Clinical and Molecular in Rectal Cancer (CMOR) Group

Project leader: Marit Hellum and Carola Henriksson

Aims:To modify and increase the sensitivity of the Calibrated Automated Thrombogram (CAT)-assay for measuring procoagulant activity of TF-bearing microvesicles (MV-TF), and apply the modified method on clinical samples.

 

“Endocytosis of extracellular vesicles”.

RRNEV groups involved: The Blood Cell Research Group, The Microvesicles and Prostate Cancer: Biomarkers and Release Mechanisms Group

Project leader: Reidun Øvstebø

Aims:To investigate endocytosis of extracellular microvesicles in non-phagocytic and phagocytic cells and to evaluate the influence of extracellular vesicles on recipient cells after internalization. The project will include a Master thesis project, which will be conducted by Lily Alice Skaaraas (start August 2015).

 

“Standardization of the use of NanoSight for the characterization of EVs”.

RRNEV groups involved: The Blood Cell Research Group, The Microvesicles and Prostate Cancer: Biomarkers and Release Mechanisms Group, Thermo Fisher – Life Sciences Group

Project leader: Beate Vestad

Aims:To standardize NanoSight analyses of selected biological EVs and commercial beads, using three different NanoSight instruments. We aim to evaluate intra- and inter-assay variation of NTA measurements of both size and concentration of different biological EVs and commercially available beads, as well as the effect of selected NTA software settings.

 

List of publications (24), relevant to EV research, 2016 – 2011

2016:

Diagnostic and prognostic relevance of circulating cell-free miRNAs in prostate cancer: a systematic review. E. Endzeliņš, V. Melne, Z. Kalniņa, V. Lietuvietis, U. Riekstiņa, A. Llorenteand A. Linē. Molecular Cancer. 2016. 15:41.
 
PIKfyve inhibition affects exosome release and secretory autophagy. N.P. Hessvik, A. Øverbye, A. Brech, M.L. Torgersen, I.S. Jakobsen, K. Sandvig and A. Llorente. Cell. Mol. Life Sci. 2016 Jul 20. Epub ahead of print. DOI:10.1007/s00018-016-2309-8.
 
S. Fais, B. Giebel, G. Camussi, F. Cappello, J. Carvalho, A. Cordeiro da Silva, R. Furlan, V. Iglic, B. Kaeffer, M.E. Lekka, T. Lener, G. Lipps,  A. Llorente, A. Marcilla, S. Marei, I. Nazarenko, L. O’Driscoll, C. Oliveira, E. Rohde, H. Vasconcelos, M.H.M. Wauben, M.L. Yliperttula, N. Zarovni, A.B. Zavec. Evidence-based consensus on the use of nanosized extracellular vesicles in nanomedicine. ACS Nano. 2016. 10:3886-99.

 

2015:

A. Øverbye, T. Skotland, C. Koehler, B. Thiede, T. Seierstad, V. Berge, K. Sandvig, A.Llorente. Identification of Prostate Cancer Biomarkers in Urinary Exosomes. Oncotarget. 2015, 6(30):30357-76.

M. Yáñez-Mó, P. Siljander, Z. Andreu, A.B. Zavec, F.E. Borràs, E.I. Buzas, K. Buzas, E. Casal, F. Cappello, J. Carvalho, E. Colás, A. Cordeiro-da Silva, S. Fais, J.M. Falcon-Perez, I.M. Ghobrial, B. Giebel, M. Gimona, M. Graner, I. Gursel, M. Gursel, N.H.H. Heegaard, A. Hendrix, P. Kierulf, K. Kokubun, M. Kosanovic, V. Kralj-Iglic, E. Kramer-Albers, S. Laitinen, C. Lässer, T. Lener, E. Ligeti, A. Line,G. Lipps, A. Llorente, J. Lötvall, M. Mancek-Keber, A. Marcilla, M. Mittelbrunn, I. Nazarenko, E.N.M. Nolte-‘t Hoen, T.A. Nyman, L. O'Driscoll, M. Olivan, C. Oliveira, É. Pállinger, J. Reventós, M. Rigau, M. Sammar, F. Sanchez Madrid, M. Stampe Ostenfeld, R. Stukelj, H.A. del Portillo, E. Rhode, N. Santarém, K. Schallmoser, W. Stoorvogel, S.G. van der Grein, M.H. Vasconcelos,  M.H.M. Wauben, O. De Wever. Biological Properties of Extracellular Vesicles and Their Physiological Functions. Journal of Extracellular Vesicles, 2015, 4:27066.

Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, García-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G, Shen TL, Labori KJ, Lothe IM, Kure EH, Hernandez J, Doussot A, Ebbesen SH, Grandgenett PM, Hollingsworth MA, Jain M, Mallya K, Batra SK, Jarnagin WR, Schwartz RE, Matei I, Peinado H, Stanger BZ, Bromberg J, Lyden D. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver, Nat Cell Biol. 2015 Jun;17(6):816-26.

S. Phuyal, T. Skotland, N.P. Hessvik, A. Øverby, A. Brech, K. Ekroos, K. Sandvig, A. Llorente. The Ether Lipid Precursor Hexadecylglycerol Stimulates the Release and Changes the Composition of Exosomes Derived from PC-3 cells. J. Biol. Chem. 2015,290:4225-37.

Pedersen, KW., Kierulf, B., Manger, I., Oksvold, MP., Li, M., Vlassov, A., Roos, N., Kullmann and Neurauter, A. Direct Isolation of Exosomes from Cell Culture: Simplifying Methods for Exosome Enrichment and Analysis. Translational Biomedicine, 2015, vol. 6 No. 2:18 (in press).

Pedersen, KW., Kierulf, B., Oksvold, MP., Li, M., Vlassov, A., Roos, N., Kullmann, A and Neurauter, A. Isolation and characterization of exosomes using magnetic beads. BioProbes 71, 2015.

M. P. Oksvold, A. Neurauter and K. W. Pedersen. Magnetic bead-based isolation of exosomes. Methods Mol Biol 2015, 1218, 465-81.

 

2014:

Hellum M, Øvstebø R, Brusletto BS, Berg JP, Brandtzaeg P, Henriksson CE. Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in meningococcal septic shock. Thromb Res. 2014 Mar;133(3):507-14. Epub 2013 Dec 29. PMID: 24423888.

Øvstebø R, Hellum M, Aass HC, Trøseid AM, Brandtzaeg P, Mollnes TE, Henriksson CE. Microparticle-associated tissue factor activity is reduced by inhibition of the complement protein 5 in Neisseria meningitidis-exposed whole blood. Innate Immun. 2014 Jul;20(5):552-60. Epub 2013 Sep 19. PMID: 24051102.

M. P. Oksvold, A. Kullmann, L. Forfang, B. Kierulf, M. Li, A. Brech, A. V. Vlassov, E. B. Smeland, A. Neurauter, K. W. Pedersen. Expression of B-cell surface antigens in subpopulations of exosomes released from B-cell lymphoma cells. Clinical Therapeutics 2014 June 36, 847-862.e1.

Phuyal S, Hessvik NP, Skotland T, Sandvig K, Llorente A. Regulation of exosome release by glycosphingolipids and flotillins. FEBS J. 2014 May;281(9):2214-27.

 

2013:

A. Llorente, T. Skotland, T. Sylvänne, T. Rog, D. Kauhanen, A. Orłowski, I. Vattulainen, K. Ekroos, K. Sandvig. Molecular Lipidomics of Exosomes Released by PC-3 Prostate Cancer Cells. Biochim. Biophys. Acta. Molecular and Cell Biology of Lipids. 2013, 1831:1302–1309.

N. P. Hessvik, K. Sandvig, A. Llorente. Exosomal miRNAs as Biomarkers for Prostate Cancer. Frontiers in Genetics. 2013, Volume 4, Article 36.

E. Zeringer, M. Li, T. Barta, J. Schageman, K. W. Pedersen, A. Neurauter, S. Magdaleno, R. Setterquist, A. V. Vlassov. Methods for the extraction and RNA profiling of exosomes. World J Methodol. 2013 March 26; 3(1): 11–18.  Published online 2013 March 26. PMCID:  MC4145569

 

2012:

Øvstebø R, Aass HC, Haug KB, Trøseid AM, Gopinathan U, Kierulf P, Berg JP, Brandtzaeg P, Henriksson CE. LPS from Neisseria meningitidis is crucial for inducing monocyte- and microparticle-associated tissue factor activity but not for tissue factor expression. Innate Immun. 2012 Aug;18(4):580-91. Epub 2011 Dec 16. PMID: 22180561.

Hellum M, Øvstebø R, Trøseid AM, Berg JP, Brandtzaeg P, Henriksson CE. Microparticle-associated tissue factor activity measured with the Zymuphen MP-TF kit and the calibrated automated thrombogram assay. Blood Coagul Fibrinolysis. 2012 Sep;23(6):520-6. PMID: 22732249.

R. J. Simpson, H. Kalra, H. Ji,  P. Altevogt, P. Askenase, X. Breakefield, E. Buzas, G. Camussi, A. Clayton, S. Gabrielsson, Y.S. Gho, R. Graca, H.C. Harsha, A. Hill, G. Jenster, L.S. Kiang, A. Llorente, F.S. Madrid, I. Nazarenko, R. Nieuwland, L.M. Nilsson, A. Pandey, S. Pluchino, T.S. Prasad, L. Rajendran, M. Record, G. Reid, W. Stoorvogel, D. Taylor, C. Thery, M. Vidal, M. Zoeller and S. Mathivanan.Vesiclepedia: A Compendium for Extracellular Vesicles that Enables Continuous Community Annotation. PLoS Biology 2012, 10(12):e1001450.

N. Hessvik, S. Phuyal, A. Brech, K. Sandvig, A. Llorente. Profiling of microRNAs in Exosomes Released from PC-3 prostate Cancer Cells. Biochim. Biophys. Acta. Gene regulatory mechanisms. 2012, 1819(11-12):1154-1163.

K. Sandvig, A. Llorente. Proteomic Analysis of Microvesicles Released by the Human Prostate Cancer Cell Line PC-3. Mol. Cell. Proteomics. 2012, 11(7):M111.012914.

 

2011:

Henriksson CE, Hellum M, Haug KB, Aass HC, Joø GB, Øvstebø R, Trøseid AM, Klingenberg O, Kierulf P. Anticoagulant effects of an antidiabetic drug on monocytes in vitro. Thromb Res. 2011 Nov;128(5):e100-6. Epub 2011 Aug 20. PMID: 21862110.

Aass HC, Øvstebø R, Trøseid AM, Kierulf P, Berg JP, Henriksson CE. Fluorescent particles in the antibody solution result in false TF- and CD14-positive microparticles in flow cytometric analysis. Cytometry A. 2011 Dec;79(12):990-9. Epub 2011 Oct 11. PMID: 21990118.

 

 

Other research disseminations, relevant to EV research, 2016 – 2011

Editorial posts:

P. Kierulf. Kreftens små budbringere [Internet]. Forskningssykehuset (blog), Forskning.no. Published 2016 Feb 02. Available from: http://forskning.no/blogg/forskningssykehuset/kreftens-sma-budbringere  

A. Llorente,R. Øvstebø. Ekstracellulære vesikler: Nye formidlere av intercellulær informasjon. NBSnytt. Published 2014, 1, 12-13. http://www.biokjemisk.no/download/nbs-nytt/2014/NBS_nytt_1_2014.pdf

A. H. Ree. Spredning av kreft via mikroblærer [Internet]. Kreftforeningen. Published 2014 Jan 01. Available from: https://kreftforeningen.no/forskning/forskningsprosjekter-vi-stotter/spredning-av-kreft-via-mikroblarer/

 

 

Oral presentations (*presenting authors):

B. Vestad. Ekstracellulære vesikler som biomarkører. Presented at Bioingeniørkongressen 2016; Oslo, Norway.

T.H.Schøyen. MikroRNA fra ekstracellulære vesikler i plasma som potensielle biomarkører. Presented at Bioingeniørkongressen 2016; Oslo, Norway.

 

Abstracts contributed to the Fourth International Meeting of the International Society of Extracellular Vesicles. Journal of Extracellular Vesicles, Supplement 1, 2015:


The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells (ORAL PRESENTATION). S. Phuyal*, T. Skotland, N. Hessvik, H. Simolin, A. Øverby, A. Brech, R. G. Parton, K. Ekroos, K. Sandvig and A. Llorente.

From basic research to clinical setting: adapting methods for EV culturing, enrichment and analysis (ORAL PRESENTATION). B. Paszkiet and A. Neurauter*.

Identification of optimal culturing conditions for studying exosomes from normoxic and hypoxic colorectal cancer cell lines (ORAL WITH POSTER). N. Sivarajah, A.H. Ree, E. Kalanxhi, K.R. Redalen, K. Risberg*.

 

 

Abstract contributed to the Second International Meeting of the International Society of Extracellular Vesicles (Boston 2013):

Microparticle-associated tissue factor activity is reduced by inhibition of the complement protein 5 in Neisseria meningitidis-exposed whole blood. (ORAL PRESENTATION) Øvstebø R*, Hellum M, Aass HC, Trøseid AM, Brandtzaeg P, Mollnes TE, Henriksson CE.

 

 

Abstract contributed to the First International Meeting of the International Society of Extracellular vesicles published in The Journal of Extracellular Vesicles, Supplement 1, 2012:


Proteomic analysis of microvesicles released by the prostate cancer cell line PC-3 (ORAL PRESENTATION). A. Llorente* and K. Sandvig.

 

 

Posters (*presenting authors):

Abstracts contributed to the Fifth International Meeting of the International Society of Extracellular Vesicles. Journal of Extracellular Vesicles, 2016 (Journal of Extracellular Vesicles 2016, 5: 31552. http://dx.doi.org/10.3402/jev.v5.31552):

Exosomes from hypoxic colorectal cancer (CRC) cells – miRNA cargo as indicator of adverse CRC biology? (POSTER). T. Bjørnetrø*.

Exosomal proteins as prostate cancer biomarkers in urine: From mass spectrometry discovery to antibody-based validation (POSTER). A. Llorente*.

Extracellular vesicles derived from SW480 cancer colon cells are internalized by human primary monocytes but not by lymphocytes (POSTER). B. Vestad*, L.A. Skaaraas, A. Llorente, K.B.F. Haug, R. Øvstebø.

CD9-positive EVs isolated from size exclusion chromatography (SEC)-precleared plasma from patients and healthy individuals reveal microRNA (miRNA) patterns (POSTER).K.B.F. Haug*, T.H. Schøyen, B. Vestad, B. Kierulf,P. Kierulf, K.W. Pedersen, A. Neurauter, E.H. Kure, R. Øvstebø.

 

 

Abstracts contributed to the Fourth International Meeting of the International Society of Extracellular Vesicles, published in Journal of Extracellular Vesicles, Supplement 1, 2015:

Haug, KBF et al (2015): Size exclusion chromatography (SEC)-preclearing of plasma from patient samples facilitates magnetic bead based isolation of CD9 or CD81 expressing circulating EVs (POSTER). K.B.F.Haug*, B.Vestad, B. Kierulf, H.C.D. Aass, P. Kierulf, K.W. Pedersen, E. Kure, A. Neurauter, R. Øvstebø.

From basic research to clinical setting: Adapting methods for EV enrichment and analysis (POSTER). A. Neurauter*, B. Kierulf, A. Kullmann and K. W. Pedersen.

 

 

Abstracts contributed to the Third International Meeting of the International Society of Extracellular vesicles published in Journal of Extracellular Vesicles, Supplement 1, 2014:


The glycosphingolipid synthesis inhibitor PDMP modulates the composition of exosomes released from PC-3 cells (POSTER). S.Phuyal*, N. P. Hessvik, T. Skotland, K. Sandvig, A. Llorente.


Size and concentration analysis of EV by Nanoparticle Tracking Analysis: A Variation study (POSTER)
B. Vestad*, A. Llorente, A. Neurauter, S. Phuyal, B. Kierulf, P.Kierulf, M. Hellum, K. B. F. Haug, R. Øvstebø.


Expression of surface antigens in subpopulations of exosomes released into the urine from prostate cancer patients (POSTER). A. Neurauter*, A. Kullmann, K. W. Pedersen, M. Oksvold.

 

 

Abstracts contributed to the Second International Meeting of the International Society of Extracellular vesicles published in Journal of Extracellular Vesicles, Supplement 1, 2013:


Molecular lipidomics analysis of exosomes released by PC-3 prostate cancer cells: implications for exosome membrane structure (POSTER). A. Llorente*, T. Skotland, T. Sylvanne2, D. Kauhanen2, K. Ekroos and K. Sandvig.


Profiling of microRNAs in exosomes from PC-3 prostate cancer cells (POSTER). N.P. Hessvik*, S. Phuyal, A. Brech, K. Sandvig and A. Llorente.

Magnetic beads for fast and reproducible isolation/characterization of exosomes based on surface protein expression. A. Neurauter*, A. Kullmann, B. Kierulf, M. P. Oksvold and K. W. Pedersen.