Proteomic Landscape of Exosomes Reveals the Functional Contributions of CD151 in Triple-Negative Breast Cancer

• Published in: Molecular & cellular proteomics Vol. 20; p. 100121
• Main Authors: Li, Sipeng, Li, Xinya, Yang, Siqi, Pi, Hao, Li, Zheyi, Yao, Pengju, Zhang, Qi, Wang, Qingsong, Shen, Pingping, Li, Xizhou, Ji, Jianguo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021; American Society for Biochemistry and Molecular Biology
• Subjects: Adult; Aged; Aged, 80 and over; Cell Line, Tumor; exosomal CD151; exosomes; Exosomes - metabolism; Female; Humans; Middle Aged; Protein Interaction Maps; Proteome - metabolism; proteomics; Tetraspanin 24 - genetics; Tetraspanin 24 - metabolism; TNBC; Triple Negative Breast Neoplasms - blood; Triple Negative Breast Neoplasms - metabolism; proteomics; TBST; exosomal CD151; DEP; PD; FDR; exosomes; FBS; NTA; TMT; TNBC; HER2; FC; TEM
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1016/j.mcpro.2021.100121

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Patients with TNBC have poor overall survival because of 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 ten patients with TNBC and 17 healthy donors to identify potential therapeutic targets. Using a tandem mass tag–based quantitative proteomics approach, we characterized the proteomes of individual patient-derived serum exosomes, identified exosomal protein signatures specific to patients with TNBC, and filtered out differentially expressed proteins. Most importantly, we found that the tetraspanin CD151 expression levels in TNBC-derived serum exosomes were significantly higher than those exosomes from healthy subjects, and we validated our findings with samples from 16 additional donors. Furthermore, utilizing quantitative proteomics approach to reveal the proteomes of CD151-deleted exosomes and cells, we found that exosomal CD151 facilitated secretion of ribosomal proteins via exosomes while inhibiting exosome secretion of complement proteins. Moreover, we 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. Our 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. [Display omitted] •Quantitative proteomics of TNBC patient serum-derived exosomes.•CD151 is significantly enriched in the TNBC patient serum-derived exosomes.•CD151 regulates the secretion of ribosomal and complement proteins via exosomes.•Exosomal CD151 promotes TNBC cell migration and invasion. Using a quantitative proteomics approach, Li et al. characterized the proteomes of triple-negative breast cancer (TNBC) patient–derived serum exosomes and found the tetraspanin CD151 to be significantly enriched. Proteomic analysis of CD151-deleted exosomes and cells showed regulation of ribosomal and complement protein secretion. CD151-deleted exosomes were shown to significantly decrease the migration and invasion of TNBC cells, indicating that exosomal CD151 may be a potential therapeutic target for TNBC.