Towards establishing extracellular vesicle-associated RNAs as biomarkers for HER2+ breast cancer

Colin L Hisey; Petr Tomek; Yohanes N S Nursalim; Lawrence W Chamley; Euphemia Leung

doi:10.12688/f1000research.27393.3

Towards establishing extracellular vesicle-associated RNAs as biomarkers for HER2+ breast cancer

F1000Res. 2020 Nov 23:9:1362. doi: 10.12688/f1000research.27393.3. eCollection 2020.

Authors

Colin L Hisey^{1

2}, Petr Tomek³, Yohanes N S Nursalim¹, Lawrence W Chamley^{1

2}, Euphemia Leung^{3

4}

Affiliations

¹ Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.
² Hub for Extracellular Vesicle Investigations, University of Auckland, Auckland, New Zealand.
³ Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand.
⁴ Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.

Abstract

Extracellular vesicles (EVs) are emerging as key players in breast cancer progression and hold immense promise as cancer biomarkers. However, difficulties in obtaining sufficient quantities of EVs for the identification of potential biomarkers hampers progress in this area. To circumvent this obstacle, we cultured BT-474 breast cancer cells in a two-chambered bioreactor with CDM-HD serum replacement to significantly improve the yield of cancer cell-associated EVs and eliminate bovine EV contamination. Cancer-relevant mRNAs BIRC5 (Survivin) and YBX1, as well as long-noncoding RNAs HOTAIR, ZFAS1, and AGAP2-AS1 were detected in BT-474 EVs by quantitative RT-PCR. Bioinformatics meta-analyses showed that BIRC5 and HOTAIR RNAs were substantially upregulated in breast tumours compared to non-tumour breast tissue, warranting further studies to explore their usefulness as biomarkers in patient EV samples. We envision this effective procedure for obtaining large amounts of cancer-specific EVs will accelerate discovery of EV-associated RNA biomarkers for cancers including HER2+ breast cancer.

Keywords: CELLine bioreactor; Extracellular vesicles; HOTAIR; exosomes; long-noncoding RNA; survivin/BIRC5.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers, Tumor / genetics
Breast Neoplasms* / genetics
Cattle
Extracellular Vesicles*
Humans
RNA, Long Noncoding* / genetics

Substances

Biomarkers, Tumor
RNA, Long Noncoding

Associated data

Dryad/10.5061/dryad.jdfn2z393

Grants and funding

EL acknowledges support from the New Zealand Breast Cancer Foundation Belinda Scott Science Fellowship. CH acknowledges support from the New Zealand Breast Cancer Foundation Technology and Innovation Grant. PT acknowledges support of the John Gavin Postdoctoral Fellowship (GOT-1717-JGPDF) from the Cancer Research Trust New Zealand. The authors acknowledge the support of the Hub for Extracellular Vesicle Investigations (HEVI) and the Auckland Cancer Society Research Centre at the University of Auckland.