Exosomes in Breast Cancer: Involvement in Tumor Dissemination and Prospects for Liquid Biopsy

Abstract

In women, breast cancer (BC) is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer death (15.5%). Understanding how this heterogeneous disease develops and the confirm mechanisms behind tumor progression is of utmost importance. Exosomes are long-range message vesicles that mediate communication between cells in physiological conditions but also in pathology, such as breast cancer. In recent years, there has been an exponential rise in the scientific studies reporting the change in morphology and cargo of tumor-derived exosomes. Due to the transfer of biologically active molecules, such as RNA (microRNA, long non-coding RNA, mRNA, etc.) and proteins (transcription factors, enzymes, etc.) into recipient cells, these lipid bilayer 30–150 nm vesicles activate numerous signaling pathways that promote tumor development. In this review, we attempt to shed light on exosomes’ involvement in breast cancer pathogenesis (including epithelial-to-mesenchymal transition (EMT), tumor cell proliferation and motility, metastatic processes, angiogenesis stimulation, and immune system repression). Moreover, the potential use of exosomes as promising diagnostic biomarkers for liquid biopsy of breast cancer is also discussed.

Liquid Biopsies: Emerging role and clinical applications in solid tumours

“…In a study on PC, exosomes in the blood and urine samples of invasive and metastatic cancer patients showed presence of PC-specific components that increase the detection specificity and sensitivity [46] . In a study on breast cancer, alterations in morphology and cargo of exosomes loaded with molecules like micro-RNAs and long noncoding RNAs were observed to be responsible for the activation of multiple aberrant signalling pathways [47] . Another study on TNBC breast cancer revealed the presence of specific miRNAs like miR246, 134, and 503 thought to be playing a significant role in tumour metastasis, and can be used as a metastatic biomarker [48] .…”

“…However, cancer detection via exosomes also has its limitations, as some miRNAs encaged in these exosomes have been observed to be common in different cancers which make it difficult to differentiate among specific cancers. Nevertheless, exosomes need to be explored further for identification and development of specific biomarkers for different cancers [47] .…”

Microfluidics‐based molecular profiling of tumor‐derived exosomes for liquid biopsy

“…15,16 Compared with the other two biomarkers, tumor-derived exosomes acted as an alternative in liquid biopsy. [17][18][19] Exosomes were typical double-lipid membrane vesicles with diameter varied from 30 to 150 nm. 20 Exosomes not only play an important role in orchestrating intercellular communication but were also regarded as invaluable biomarker candidates for the early diagnosis of cancer in light of their biocompatible nature.…”

“…The typical components in the sample of liquid biopsy include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and circulating vesicle structure, which were released from the primary cells and metastasis 15,16 . Compared with the other two biomarkers, tumor‐derived exosomes acted as an alternative in liquid biopsy 17–19 . Exosomes were typical double‐lipid membrane vesicles with diameter varied from 30 to 150 nm 20 .…”

Regulation of Extracellular Vesicle-Mediated Immune Responses against Antigen-Specific Presentation

“…Extracellular vesicles (EVs) are lipid bilayer structures secreted by living cells and are classified into either exosomes, microvesicles (MVs), or apoptotic bodies, based on the intracellular production mechanism and size ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , …”