Pancreatic Pre-malignant Lesions Secrete TIMP1, Which Activates Hepatic Stellate Cells Via CD63 Signaling to Create a Pre-Metastatic Niche in the Liver

Pancreatic ductal adenocarcinoma (PDAC) metastasizes to liver at early stages, making this disease highly lethal. TIMP metallopeptidase inhibitor 1 (TIMP1) creates a metastasis-susceptible environment in the liver. We investigated the role of TIMP1 and its receptor CD63 in metastasis of early-stage pancreatic tumors using mice and human cell lines and tissue samples.