The Role of Exosomes in Breast Cancer

Abstract

BACKGROUND Although it has been long realized that eukaryotic cells release complex vesicular structures into their environment, only in recent years has it been established that these entities are not merely junk or debris, but that they are tailor-made specialized minimaps of their cell of origin and of both physiological and pathological relevance. These exosomes and microvesicles (ectosomes), collectively termed extracellular vesicles (EVs), are often defined and subgrouped first and foremost according to size and proposed origin (exosomes approximately 30–120 nm, endosomal origin; microvesicles 120–1000 nm, from the cell membrane). There is growing interest in elucidating the relevance and roles of EVs in cancer. CONTENT Much of the pioneering work on EVs in cancer has focused on breast cancer, possibly because breast cancer is a leading cause of cancer-related deaths worldwide. This review provides an in-depth summary of such studies, supporting key roles for exosomes and other EVs in breast cancer cell invasion and metastasis, stem cell stimulation, apoptosis, immune system modulation, and anti–cancer drug resistance. Exosomes as diagnostic, prognostic, and/or predictive biomarkers and their potential use in the development of therapeutics are discussed. SUMMARY Although not fully elucidated, the involvement of exosomes in breast cancer development, progression, and resistance is becoming increasingly apparent from preclinical and clinical studies, with mounting interest in the potential exploitation of these vesicles for breast cancer biomarkers, as drug delivery systems, and in the development of future novel breast cancer therapies.

Characterization of the release and biological significance of cell-free DNA from breast cancer cell lines

“…For the undigested cfDNA, cells might have some protective mechanism. Some studies have shown that cancer cells actively secrete cfDNA into the blood circulation in different forms, such as in exosomes, and the cfDNA inside these carriers could be protected from degradation [12, 14]. Our results also suggested that breast cancer cells in G1 phase secrete more exosomes.…”

“…For example, microRNAs in blood have important functions in tumorigenesis, metastasis and resistance [14]. However, there are very few reports on the effects of cfDNA on cancer cells.…”

Analysis of circulating tumor DNA in breast cancer as a diagnostic and prognostic biomarker

“…It is believed that dysregulation in this communication is involved in pathogenesis of cancer. It has been shown that exosomes play an important role in cancer cell invasion and metastasis, stem cell stimulation, angiogenesis, apoptosis, interaction with immune system cells, and drug resistance [102,103]. Hannafon et al reported selective encapsulation or elevated enrichment of certain microRNAs in exosomes release in the bloodstream of patients with breast cancer [104], and other studies have reported elevated CEA and CA 15-3 in the exosomes of such patients [103].…”

Exosome: An Emerging Participant in the Development of Liver Disease

“…Thus, exosomes and their contents may be used as novel potential biological markers for disease diagnosis and prognosis, as a vehicle for drug intervention and RNA interference therapy, or as a potential target for clinical treatment. For instance, exosomes play a functional role in myocardial remodeling (1), Alzheimer disease (AD) (2), breast cancer (3,4), and other cancers (5-7).…”