Peacock, B., Rigby, A., Bradford, J. orcid.org/0000-0002-7771-914X et al. (4 more authors) (2018) Extracellular vesicle microRNA cargo is correlated with HPV status in oropharyngeal carcinoma. Journal of Oral Pathology and Medicine, 47 (10). pp. 954-963. ISSN 0904-2512
Abstract
Background
The incidence of human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has increased rapidly in recent decades. These tumours have a favourable outcome compared to HPV‐negative (HPV−) OPSCC. However, HPV+ tumours are more likely to metastasise to distant sites, suggesting a difference in how these tumour subtypes interact with the metastatic niche. Extracellular vesicles (EVs) have emerged as important players in cell‐to‐cell communication and are a potential source of biomarkers for cancer diagnosis. This study aims to characterise the microRNA cargo of small EVs released by HPV+ and HPV− OPSCC cell lines.
Methods Extracellular vesicles produced by HPV+ (SCC2 and SCC90) and HPV− (SCC72 an SCC89) OPSCC cells were characterised by tunable resistive pulse sensing (TRPS) and western blotting. RNA was extracted from EVs and analysed by small RNA sequencing. A bioinformatics approach was used to identify EV miRNA signatures associated with HPV status.
Results HPV− OPSCC cells produced more EVs than HPV+ OPSCC cells. EVs were positive for the common EV markers CD63, CD9 and TSG101. Unbiased hierarchical clustering analysis of EV miRNA cargo revealed that samples clustered based on HPV status. 14 miRNA were enriched in HPV+ cell‐derived EVs, whereas 19 miRNA were enriched in EVs derived from HPV− cell lines.
Conclusions Here, we identify EV miRNA signatures indicative of the HPV status of the parent cell. This may provide a platform from which to validate salivary or blood‐based biomarkers with utility for early detection and stratifying risk in OPSCC patients.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 John Wiley & Sons A/S. This is an author produced version of a paper subsequently published in Journal of Oral Pathology and Medicine. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Extracellular vesicles; head and neck cancer; human papillomavirus; microRNA; oropharyngeal carcinoma |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Jan 2019 13:45 |
Last Modified: | 23 Sep 2019 00:39 |
Published Version: | https://doi.org/10.1111/jop.12781 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/jop.12781 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:140646 |