title: From tissue turnover to the cell of origin for pancreatic cancer.
abstract: The identity of the cell of origin for pancreatic ductal adenocarcinoma (PDAC) has long been debated. PDAC has a ductal morphology, but there is no formal proof that it originates from the ductal compartment. Targeting Kras expression to adult acinar or endocrine lineages induces the formation of tumors reminiscent of human PDAC, but only in the presence of concomitant inflammation. Apart from cells of the Pdx1-positive lineage in the adult pancreas, which can be transformed (albeit with low frequency), the cells susceptible to acquiring or retaining oncogenic mutations remain elusive. Hypothetically, a subset of cells that renew the adult organ physiologically or regenerate it upon severe tissue damage would be more susceptible to oncogenic transformation than mature, differentiated cells. Such a compartment could consist of putative pancreatic stem cells, progenitor cells, facultative stem cells or transdifferentiated bone marrow cells. An integrated approach combining techniques from stem cell and cancer biology will be necessary to define and map these cells.
authors.affiliation: Department of Surgery, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: Bo
authors.initials: B
authors.lastname: Kong
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.forename: Mert
authors.initials: M
authors.lastname: Erkan
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D006801:Humans; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology