The Role of Exosomes in Breast Cancer Diagnosis

Abstract

The importance of molecular re-characterization of metastatic disease with the purpose of monitoring tumor evolution has been acknowledged in numerous clinical guidelines for the management of advanced malignancies. In this context, an attractive alternative to overcome the limitations of repeated tissue sampling is represented by the analysis of peripheral blood samples as a ‘liquid biopsy’. In recent years, liquid biopsies have been studied for the early diagnosis of cancer, the monitoring of tumor burden, tumor heterogeneity and the emergence of molecular resistance, along with the detection of minimal residual disease. Interestingly, liquid biopsy consents the analysis of circulating tumor cells, circulating tumor DNA and extracellular vesicles (EVs). In particular, EVs play a crucial role in cell communication, carrying transmembrane and nonmembrane proteins, as well as metabolites, lipids and nucleic acids. Of all EVs, exosomes mirror the biological fingerprints of the parental cells from which they originate, and therefore, are considered one of the most promising predictors of early cancer diagnosis and treatment response. The present review discusses current knowledge on the possible applications of exosomes in breast cancer (BC) diagnosis, with a focus on patients at higher risk.

Exosomes: A Forthcoming Era of Breast Cancer Therapeutics

“…Additionally, it also provides us an opportunity to explore biomarkers for better diagnosis and prognosis at an early stage [ 166 , 167 ]. In 2016, two test kits on fluid biopsy-based approaches were available to detect prostate and lung diseases (ExoDx ® prostate and ExoDx ® Lung, Exosome Diagnostics Inc., Waltham, MA, U.S.A) [ 87 , 168 , 169 ]. Breast cancer-derived exosomes have also been considered as a potential indicator of cancer progression [ 114 ].…”

Circulating and Intracellular miRNAs as Prognostic and Predictive Factors in HER2-Positive Early Breast Cancer Treated with Neoadjuvant Chemotherapy: A Review of the Literature

“…EVs are involved in several biological processes such as antigen presentation, immune regulation, apoptosis evasion, drug resistance, and angiogenesis [ 25 , 26 , 27 , 28 ]. Based on their size, they are classified into apoptotic bodies (50–5000 nm) released by apoptotic cells, shedding microvesicles/ectosomes (100–1000 nm) produced by budding from the plasma membrane, and exosomes (30–150 nm) that originate from intracellular multivesicular bodies and are secreted in the extracellular space upon fusion with the plasma membrane [ 20 , 23 , 29 ]. They carry proteins, metabolites, lipids, mRNA, miRNA, long-non-coding RNA, and DNA [ 24 , 25 , 26 , 30 , 31 ].…”

“…In particular, miRNAs secreted by cancer cells are packed into extracellular vesicles (EVs) and released into peripheral blood. EVs are largely involved in the cross-talk between cancer cells and the microenvironment [ 20 , 21 ]. The important involvement of EVs and miRNA in ontogenetic processes and their availability in biological fluids, make these molecules optimal biomarkers in oncology [ 20 , 22 ].…”

Characterization of Exosome-Related Gene Risk Model to Evaluate the Tumor Immune Microenvironment and Predict Prognosis in Triple-Negative Breast Cancer

“…As a type of extracellular vesicles (EVs), exosomes are homogenous membrane vesicles (ranging from 30 to 150 nm), derived from the multivesicular bodies (MVBs), formed by the budding of the endosomal membranes and released in the extracellular space upon fusion with the plasma membrane (7,8). In 1983, exosomes were discovered and considered to operate as cellular garbage disposal (9,10).…”

“…In 1983, exosomes were discovered and considered to operate as cellular garbage disposal (9,10). With the investigation of biological function, angiogenesis, immunity, and metastasis have been demonstrated to be regulated by exosomes from cancer cells, making a critical effect in facilitating tumorigenesis (8,11,12). Interestingly, some studies indicated that one part of the human epidermal growth factor receptor (HER) family was exosome associated in breast, gastric, and pancreatic cancers (8,(13)(14)(15).…”