Proteomic landscape of exosomes reveals the functional contributions of CD151 in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Patients with TNBC have poor overall survival due to limited molecular therapeutic targets. Recently, exosomes have been recognized as key mediators in cancer progression, but the molecular components and function of TNBC-derived exosomes remain unknown. The main goal of this study was to reveal the proteomic landscape of serum exosomes derived from 10 TNBC patients and 17 healthy donors to identify potential therapeutic targets. Using a tandem mass tag (TMT)-based quantitative proteomics approach, Peking University researchers characterized the proteomes of individual patient-derived serum exosomes, identified exosomal protein signatures specific to TNBC patients, and filtered out differentially expressed proteins (DEPs). Most importantly, the researchers found that CD151 expression levels in TNBC-derived serum exosomes were significantly higher than those exosomes from healthy subjects, and they validated their findings with samples from 16 additional donors. Furthermore, utilizing quantitative proteomics approach to reveal the proteomes of CD151-deleted exosomes and cells, the researchers found that exosomal CD151 facilitated secretion of ribosomal proteins via exosomes while inhibiting exosome secretion of complement proteins. Moreover, they proved that CD151-deleted exosomes significantly decreased the migration and invasion of TNBC cells. This is the first comparative study of the proteomes of TNBC patient-derived and CD151-deleted exosomes. These findings indicate that profiling of TNBC-derived exosomal proteins is a useful tool to extend our understanding of TNBC, and exosomal CD151 may be a potential therapeutic target for TNBC.