Abstract
Esophageal squamous cell carcinoma (ESCC) is invasive cancer and the complex mechanisms underlying carcinogenesis remain unclear. Extracellular vesicles (EVs), secreted by most cell types, serve as a critical factor in tumorigenesis via intercellular communications. Our study aims to investigate the cellular origin of EVs in ESCC, and unveil the unknown molecular and cellular mechanisms underlying cell-cell communications. Six ESCC patients were enrolled and single-cell RNA sequencing (scRNA-seq) analyses were conducted to screen different cell subpopulations. The genetic origin of EVs was tracked using the supernatant from different cellular extracts. Nanoparticle tracking analysis (NTA), western blot analysis, and transmission electron microscopy (TEM) were performed for validation. Using scRNA-seq analysis, eleven cell subpopulations were identified in ESCC. Differences in gene expression in EVs between malignant and non-malignant esophageal tissues were found. Our findings demonstrated that epithelial cells releasing EVs were the most prevalent in malignant tissues, while endothelial cells and fibroblasts releasing EVs were predominant in non-malignant tissues. Furthermore, the high levels of gene expression in EVs released from these cells were correlated significantly with a worse prognosis. Our findings revealed the genetic origin of EVs in malignant and non-malignant esophageal tissues and provided a comprehensive overview of the associated cell-cell interactions in ESCC.