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Review

Extracellular Vesicle Dissemination of Epidermal Growth Factor Receptor and Ligands and Its Role in Cancer Progression

by 1,2,3,* and 1,2,3,4,5,*
1
Cancer Bio-Engineering Group, Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland
2
School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
3
National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, D12 8MGH Dublin, Ireland
4
Trinity Centre for Bioengineering, Trinity College Dublin, D02 8QV2 Dublin, Ireland
5
Advanced Materials and Bioengineering Research Centre (AMBER), RCSI University of Medicine and Health Sciences and Trinity College Dublin, D02 8PVW Dublin, Ireland
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(11), 3200; https://doi.org/10.3390/cancers12113200
Received: 5 October 2020 / Revised: 23 October 2020 / Accepted: 27 October 2020 / Published: 30 October 2020
Overexpression of the transmembrane protein, epidermal growth factor receptor (EGFR), drives tumour progression in several cancers including breast, lung, glioblastoma and head and neck cancers. In recent years, it has been shown that tumour cells can transfer EGFR to other tumour cells and non-tumour cells using extracellular vesicles (EVs). EVs are nano-sized vesicles secreted by cells and contain protein, RNA and DNA. The function of EVs is to send messages between cells which occurs in both healthy and diseased states. In this review, we will discuss how the transfer of EGFR and EGFR ligands by EVs in cancer can promote metastases, the formation of new tumour blood vessels and decrease the anti-tumour activity of immune cells. We will also discuss how EGFR contained in EVs can be used as a non-invasive diagnostic marker of cancer, and finally, how EVs can be re-engineered to promote targeting to EGFR expressing tumours.
The epidermal growth factor receptor (EGFR) pathway functions through the autocrine or paracrine activation of cellular EGFR by a number of transmembrane ligands. Amplified or mutant EGFR can lead to tumour formation due to increased cell proliferation, growth, migration and survival signals. These oncogenic effects were thought to be confined to aberrant cells hosting genetic alterations in EGFR. However, in the past decade, numerous studies identified that tumour cells could harness extracellular vesicles (EVs) to disseminate EGFR, mutant EGFR, phosphorylated EGFR and EGFR ligands to local and distant cells. This functions to impart a pro-tumourigenic phenotype in recipient cells. EVs play an essential role in intracellular communication, through receptor signalling or the release of their intra-vesicular content into recipient cells. This review will discuss the role of EVs delivering EGFR or EGFR ligands either to or from tumour cells and how this can promote metastases, pre-metastatic niche formation, osteoclastogenesis, angiogenesis and immune modulation in cancer. We will examine how circulating EVs positive for EGFR may be exploited as diagnostic, prognostic or therapeutic markers in cancers including breast, lung, glioblastoma, ovarian and prostate. Finally, we will explore recent breakthroughs in bio-engineering EVs with EGFR targeting abilities for targeted drug delivery. View Full-Text
Keywords: exosome; tumour progression; immune system; metastases; angiogenesis; osteoclastogenesis; biomarker; bio-engineering exosome; tumour progression; immune system; metastases; angiogenesis; osteoclastogenesis; biomarker; bio-engineering
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MDPI and ACS Style

Frawley, T.; Piskareva, O. Extracellular Vesicle Dissemination of Epidermal Growth Factor Receptor and Ligands and Its Role in Cancer Progression. Cancers 2020, 12, 3200. https://doi.org/10.3390/cancers12113200

AMA Style

Frawley T, Piskareva O. Extracellular Vesicle Dissemination of Epidermal Growth Factor Receptor and Ligands and Its Role in Cancer Progression. Cancers. 2020; 12(11):3200. https://doi.org/10.3390/cancers12113200

Chicago/Turabian Style

Frawley, Thomas, and Olga Piskareva. 2020. "Extracellular Vesicle Dissemination of Epidermal Growth Factor Receptor and Ligands and Its Role in Cancer Progression" Cancers 12, no. 11: 3200. https://doi.org/10.3390/cancers12113200

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