AUTHOR=Caplan Leah R. , Vavinskaya Vera , Gelikman David G. , Jyotsana Nidhi , Trinh Vincent Q. , Olive Kenneth P. , Tan Marcus C. B. , DelGiorno Kathleen E. TITLE=Enteroendocrine Cell Formation Is an Early Event in Pancreatic Tumorigenesis JOURNAL=Frontiers in Physiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.865452 DOI=10.3389/fphys.2022.865452 ISSN=1664-042X ABSTRACT=
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of only 11%, due, in part, to late diagnosis, making the need to understand early events in tumorigenesis critical. Acinar-to-ductal metaplasia (ADM), when not resolved, is a PDAC precursor. Recently, we showed that ADM is constituted by a heterogenous population of cells, including hormone-producing enteroendocrine cells (EECs: gamma, delta, epsilon, and enterochromaffin cells). In this study, we employed histopathological techniques to identify and quantify the abundance of EEC subtypes throughout pancreatic tumorigenesis in mouse models and human disease. We found that EECs are most abundant in ADM and significantly decrease with lesion progression. Co-immunofluorescence identifies distinct lineages and bihormonal populations. Evaluation of EEC abundance in mice lacking