Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer

Cells

Emma McDermott¹  Peter Dockery¹  Carmel Malone²  DoireannP. Joyce²  Mohamed Elhadi²  Erin Naughton²  RóisínM. Dwyer²  AndreaB. Grealish²  RonanM. Waldron²  MichaelJ. Kerin²  KillianP. O’Brien²  KatieE. Gilligan²  BrianM. Moloney²  ClodaghP. O’Neill²  ClaireL. Glynn²  Sonja Khan²  CiaránM. Maguire³  Adriele Prina-Mello³  Thomas Ritter⁴  Emma Holian⁵ 

[1]Centre for Microscopy and Imaging, Discipline of Anatomy, School of Medicine, National University of Ireland Galway, Galway H91 YR71, Ireland

[2]Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway H91 YR71, Ireland

[3]Laboratory for Biological Characterisation of Advanced Materials (LBCAM) and Advanced Materials and Bioengineering Research (AMBER) Centre, Trinity Translational Medicine Institute, Trinity College Dublin, James Street, Dublin D08 W9RT, Ireland

[4]Regenerative Medicine Institute, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway H91 YR71, Ireland

[5]School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway H91 YR71, Ireland

关键词: breast cancer;    extracellular vesicles;    exosomes;    microrna;    biomarker;    ev characterization;   

DOI  :  10.3390/cells9010141

来源: DOAJ

【 摘 要 】

Extracellular vesicles (EVs) shuttle microRNA (miRNA) throughout the circulation and are believed to represent a fingerprint of the releasing cell. We isolated and characterized serum EVs of breast tumour-bearing animals, breast cancer (BC) patients, and healthy controls. EVs were characterized using transmission electron microscopy (TEM), protein quantification, western blotting, and nanoparticle tracking analysis (NTA). Absolute quantitative (AQ)-PCR was employed to analyse EV-miR-451a expression. Isolated EVs had the appropriate morphology and size. Patient sera contained significantly more EVs than did healthy controls. In tumour-bearing animals, a correlation between serum EV number and tumour burden was observed. There was no significant relationship between EV protein yield and EV quantity determined by NTA, highlighting the requirement for direct quantification. Using AQ-PCR to relate miRNA copy number to EV yield, a significant increase in miRNA-451a copies/EV was detected in BC patient sera, suggesting potential as a novel biomarker of breast cancer.

【 授权许可】

Unknown