Proteomic profiling of extracellular vesicles allows for human breast cancer subtyping

Abstract

Extracellular vesicles (EVs) are a potential source of disease-associated biomarkers for diagnosis. In breast cancer, comprehensive analyses of EVs could yield robust and reliable subtype-specific biomarkers that are still critically needed to improve diagnostic routines and clinical outcome. Here, we show that proteome profiles of EVs secreted by different breast cancer cell lines are highly indicative of their respective molecular subtypes, even more so than the proteome changes within the cancer cells. Moreover, we detected molecular evidence for subtype-specific biological processes and molecular pathways, hyperphosphorylated receptors and kinases in connection with the disease, and compiled a set of protein signatures that closely reflect the associated clinical pathophysiology. These unique features revealed in our work, replicated in clinical material, collectively demonstrate the potential of secreted EVs to differentiate between breast cancer subtypes and show the prospect of their use as non-invasive liquid biopsies for diagnosis and management of breast cancer patients.

Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblasts

“…Proteome studies on EVs have focused on cancer, in which high numbers of EVs containing many more proteins are produced [ 31 , 36 , 37 ]. We identified over 1000 proteins in small EVs purified from conditioned media and confirmed the presence of EV marker proteins.…”

Microvesicles in Cancer: Small Size, Large Potential

“…Importantly, it has to be considered that the overexpression of certain oncogenes might impact MV protein profiles as was shown for breast cancer for the oncogene Src for Exo [124] or Her2/Neu, which was shuttled along with its associated proteins onto MV and Exo [125]. The resulting specific signatures have already been successfully used for the correct determination of breast cancer subtypes from serum EV [126]. Compared to soluble cancer biomarkers, which often suffer from low specificity and a high rate of false positive results, the strength of MV is their potential as biomarker platforms that simultaneously carry multiple markers, allowing for the recognition and detection of specific patterns.…”

Extracellular Vesicles as an Efficient and Versatile System for Drug Delivery

“…Red blood cell extracellular vesicles (RBCEVs) display surface glycophorin A, a well-known RBC marker while mesenchymal stem cell (MSC)-derived EVs exhibit surface CD73, CD90, and CD105 expression pattern [ 98 , 99 , 100 ]. Besides tracing the EV origin, researchers are also exploring the possibility of using cell-type-specific proteins on EVs to discriminate disease subtypes and to predict disease prognosis [ 101 , 102 ]. EV online databases such as Vesiclepedia [ 103 ] and ExoCarta [ 104 ] contain over thousands of EV protein entries, allowing for a conglomerate of EV protein knowledge.…”