Exosome proteomes reveal glycolysis-related enzyme enrichment in primary tumors

Abstract

Objective In this study, we aimed to identify differentially expressed exosomal proteins from primary tumor and metastases. Methods We clearly distinguished primary tumors (CHMp) from metastases (CHMm) and profiled the proteins within their secreted exosomes using LC-MS/MS. Moreover, the abundance of glycolysis enzymes (GPI, LDHA) was verified with Western blotting, and we extended to human colorectal cancer-derived exosomes (SW480 vs. SW620) for comparison. Results Among all the exosomal proteins derived from primary tumor and metastases, 87 and 63 proteins, respectively, exhibited significant differences. Notably, glycolysis enzymes (GPI, LDHA, LDHB, TPI1, and ALDOA) were specifically enriched in exosomal proteins from primary tumor. Conclusion We reported significant differences in the proteome at the cellular level between primary tumors and metastases, and intriguingly, we found this heterogeneity was mirrored in the protein composition of exosomes. We discovered that glycolysis enzymes were significantly enriched in CHMp exosomes compared to CHMm exosomes. We further demonstrated that this quantitative difference in glycolysis enzymes persisted across primary and metastatic cancers, extending to human colorectal cancer-derived exosomes (SW480 vs. SW620). Our findings of the specific enrichment of glycolysis enzymes in primary tumor-derived exosomes contribute to a better understanding of tumor microenvironment modulation and heterogeneity between primary tumors and metastases.