Cathepsin B and D drive the fibrogenic potential of pancreatic stellate cells and modulate the stromal compartment in pancreatic ductal adenocarcinoma (PDAC)

Aim: Remodelled extracellular matrix (ECM) has been implicated in the resistance of cancer cells to chemotherapy. Stromal-cell-derived proteases, e.g. cathepsins, are involved in tumorigenesis and tissue invasion but their role in regulating pancreatic stellate cells (PSCs) and thus ECM-formation is unknown. We studied whether cathepsin B and D, lysosomal proteases both highly expressed in pancreatic cancer, contribute to fibrogenesis by activating PSCs. Material and method: Cathepsin B and D activity was measured in serum of PDAC patients. PSCs were isolated by Nycodenz-gradient from mouse pancreas for immunobl…