Inflammation-driven persistent transcriptional reprogramming of the ductal epithelium in pancreatic cancer
Inflammatory exposure can induce persistent transcriptional reprogramming, thereby promoting tumorigenesis. To investigate how inflammation influences tumor-intrinsic oncogenic processes, we established organoids derived from normal and inflamed pancreatic ductal tissues obtained from patients with pancreatic cancer. Our findings show that, even in the absence of exogenous inflammatory factors, inflammatory pancreatic ductal organoids exhibit higher levels of STAT3 phosphorylation, upregulated expression of STAT3-regulated genes, and greater proliferative capacity than normal organoids. Relative to control organoids, inflammatory pancreatic ductal organoids also display pronounced ECM-like and inflammation-like alterations.