Abstract / Summary
Pancreatic ductal adenocarcinoma (PDAC) progression is driven by complex cellular interactions within the tumor microenvironment (TME), where endothelial cell (EC)-tumor-associated macrophage (TAM) crosstalk significantly influences angiogenesis and immune modulation, although the specific subsets and consequences remain unclear. Here, we integrated four single-cell RNA sequencing datasets (50 PDAC; 21 normal adjacent tissues) to profile EC and macrophage subpopulations, subsequently employing CellChat to decipher intercellular communication networks and identify altered ligand–receptor interactions in PDAC. Correlation and Kaplan–Meier survival analyses (TCGA-PAAD) assessed associations and prognostic value, while functional validation used EdU, CCK-8, and Transwell assays on PDAC cells. We identified a distinct endothelial subset (EC0) and macrophage subset (Mac2) with enhanced interaction signals in PDAC. This EC0–Mac2 crosstalk correlated with significant S100A6 upregulation, which was associated with poor patient prognosis. Exogenous S100A6 treatment markedly enhanced PDAC cell proliferation and migration in vitro. In conclusion, EC-Mac crosstalk may promote PDAC progression via S100A6, and this interaction pattern warrants further investigation as a candidate prognostic biomarker and potential target for disrupting stromal communication.