S158 Coronin 1C Promotes Desmoplastic Reaction in PDAC

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging oncological issues due to its extensive desmoplastic reaction. The desmoplastic reaction contributes to tumor progression, immune evasion, and resistance to therapy. Tumor stromal heterogeneity is influenced by the coronin family of proteins, which regulates signal transduction, cytoskeletal remodeling, transcriptional regulation, and vesicular trafficking. However, the role of coronin 1C in stromal remodeling and fibroblast activation remains poorly understood. Methods: Our study aims to investigate the expression of coronin 1C in PDAC tissues and its correlation with desmoplastic reaction. We included 51 PDAC patients and 18 normal pancreas samples obtained from road traffic accident cases. FAPI PET/CT imaging was used to assess tumor-associated fibroblast activity, which drives desmoplasia through secretion of extracellular matrix proteins. Formalin-fixed paraffin-embedded serial sections underwent immunohistochemistry for coronin 1C, CD8, and α-SMA. Masson's Trichrome staining was used to visualize collagen, and quantification was performed using ImageJ. For functional validation, MIAPaCa-2 and ASPC-1 cell lines were used, and coronin 1C knockdown was achieved via CORO1C siRNA, and its effect on α-SMA activation was assessed by qRT-PCR and Western blotting. Ex vivo slice cultures of human biopsy PDAC tissue were subjected to coronin 1C knockdown, and the resulting desmoplastic response was evaluated by assessing changes in stromal activation markers. Results: Coronin 1C was significantly overexpressed in PDAC tissues compared to normal pancreas. High coronin 1C levels correlated with elevated α-SMA expression and increased collagen deposition (P < 0.01). In vitro, silencing of coronin 1C in PDAC cell lines led to downregulation of α-SMA. Serial section immunohistochemistry study in ex vivo slice cultures indicated that coronin 1C knockdown led to decreased desmoplastic features. Conclusion: Our study demonstrates that coronin 1C contributes to desmoplastic reaction in PDAC. Targeting coronin 1C may represent a promising therapeutic strategy to remodel the PDAC tumor microenvironment and enhance treatment efficacy.