Cancer-derived exosomal DPP3 promotes lung metastasis by activating the RAP1 signaling pathway

Metastasis is the leading cause of breast cancer-related death, with lung metastasis occurring in more than 60% of breast cancer (BRCA) patients. Small extracellular vesicles (sEVs) play crucial roles in breast cancer metastasis. Dipeptidyl peptidase 3 (DPP3) is an enzyme that hydrolyzes various peptides, and its dysregulation contributes to multiple pathology processes. However, the role of DPP3 in breast cancer lung metastasis is poorly understood. In this study, we discovered a novel mechanism whereby DPP3, packaged in small extracellular vesicles (sEVs) from breast cancer, is delivered to lung tissue to remodel the vascular niche to promote lung metastasis. Overall design: To investigate the mechanism of breast cancer-secreted exosomal DPP3 on lung metastasis, we subcutaneously injected MDA-MB-231 and MDA-MB-231/DPP3 KO cells into the fourth mammary fat pat of NSG mice to construct orthotopic xenograft.After 5 weeks, mice were sacrificed, and lung tissue was collected for gene expression profiling analysis.