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From tissue turnover to the cell of origin for pancreatic cancer

Nature Reviews Gastroenterology & Hepatology volume 8, pages 467–472 (2011)Cite this article

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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.

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Figure 1: Current hypotheses that explain tissue turnover in the adult pancreas.

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Authors and Affiliations

  1. Department of Surgery, Technische Universität München, Ismaningerstrasse 22, Munich, 81675, Germany

    Bo Kong, Christoph W. Michalski, Mert Erkan, Helmut Friess & Jörg Kleeff

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B. Kong, C. W. Michalski, M. Erkan, H. Friess and J. Kleeff reviewed the literature and drafted the manuscript. All authors approved the final version of the paper.

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Correspondence to Christoph W. Michalski.

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Kong, B., Michalski, C., Erkan, M. et al. From tissue turnover to the cell of origin for pancreatic cancer. Nat Rev Gastroenterol Hepatol 8, 467–472 (2011). https://doi.org/10.1038/nrgastro.2011.114

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