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Significance We describe here the most comprehensive analyses of extracellular matrix (ECM) of pancreatic ductal adenocarcinoma (PDAC) yet available, which detected previously unknown molecular changes during PDAC progression in both mouse models and human patients. These data distinguish ECM proteins produced by tumor cells from those produced by stromal cells and show that it is the diverse set of tumor cell-derived proteins that correlate best with poor patient survival. In contrast, the stroma-derived ECM proteins, which comprise the bulk of the microenvironmental ECM, include both proteins correlating with good survival and proteins correlating with poor survival. These data may help explain why prior nonselective depletion of the stroma led to poorer patient outcomes and suggest more precise ECM manipulations as PDAC treatments.

Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells