Disputed paternity: the uncertain ancestry of pancreatic ductal neoplasia

Abstract

In this issue of Cancer Cell, Kopp and colleagues report that pancreatic ductal cells are largely refractory to the induction of pancreatic neoplasia. Whereas a rare ductal subpopulation may still prove capable of neoplastic transformation, these findings refocus attention on acinar and other non-ductal cell types as initiators of this deadly neoplasm.

Fig. 1

Competence of individual pancreatic cell types to generate pancreatic intraepithelial neoplasia (PanIN) in response to oncogenic Kras activation. Red indicates cell types capable of forming PanIN, yellow indicates cells resistant to PanIN, and grey indicates known and potentially unknown cell populations still unevaluated. A, Kras activation in early pancreatic progenitor cells and their progeny leads to effective PanIN initiation. B, Kras activation in later exocrine-dedicated progenitor cells and their acinar cell progeny also results in PanIN. C, Kras activation in differentiated acinar cells, but not the most common ductal epithelial lineage, leads to effective PanIN initiation. In an inflammatory microenvironment, insulin-expressing endocrine cells can also generate PanIN. Low-abundance pancreatic ductal/centroacinar subpopulations may still remain to be evaluated as effective cells of origin.