Dissecting the cellular origins of pancreatic cancer

Although putative premalignant lesions like metaplasia-the replacement of one mature cell type with another-have been identified in a variety of cancers, the normal cellular targets of malignant transformation are largely unknown. Pancreatic ductal adenocarcinoma (PDAC) is a particularly aggressive and lethal cancer. Despite its ductal histology, however, it is unknown whether PDAC originates from pancreatic ducts or another cell type within the pancreas. Recent analysis of mice with pancreas-specific deletion of the PTEN tumor suppressor gene has provided new insight into the mechanism of metaplasia and focuses attention on pancreatic centroacinar cells as candidates for the cellular origin of PDAC. Characterization of the cell-of-origin could lead to a better understanding of the molecular substrate for tumor initiation and eventually to early diagnosis and treatment.