Cited by 346Pancreatic and Hepatic Oncology ResearchPancreatic function and diabetesCancer Cells and Metastasis

Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates

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Means, Anna L., Meszoely, Ingrid M., Suzuki, Kazufumi, Miyamoto, Yoshiharu, Rustgi, Anil K., Coffey, Robert J., Wright, Christopher V. E., Stoffers, Doris A. +1 more·2005·Development

Abstract

Epithelial metaplasia occurs when one predominant cell type in a tissue is replaced by another, and is frequently associated with an increased risk of subsequent neoplasia. In both mouse and human pancreas, acinar-to-ductal metaplasia has been implicated in the generation of cancer precursors. We show that pancreatic epithelial explants undergo spontaneous acinar-to-ductal metaplasia in response to EGFR signaling, and that this change in epithelial character is associated with the appearance of nestin-positive transitional cells. Lineage tracing involving Cre/lox-mediated genetic cell labeling reveals that acinar-to-ductal metaplasia represents a true transdifferentiation event, mediated by initial dedifferentiation of mature exocrine cells to generate a population of nestin-positive precursors, similar to those observed during early pancreatic development. These results demonstrate that a latent precursor potential resides within mature exocrine cells, and that this potential is regulated by EGF receptor signaling. In addition, these observations provide a novel example of rigorously documented transdifferentiation within mature mammalian epithelium, and suggest that plasticity of mature cell types may play a role in the generation of neoplastic precursors.

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  • In mice, adult acinar cells can de-differentiate to a progenitor-like state with ductal appearance, termed acinar-to-ductal metaplasia (ADM).

    “murine acinar cells can de-differentiate to a progenitor-like state with a ductal appearance. This has been termed acinar-to-ductal-metaplasia (ADM)110,111”

    From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [110]

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Authors
Means, A. L., Meszoely, I. M., Suzuki, K., Miyamoto, Y., Rustgi, A. K., Coffey, R. J., Wright, C. V. E., Stoffers, D. A., & Leach, S. D.
Affiliations
  • Vanderbilt University (US)
  • Johns Hopkins University (US)
  • Abramson Cancer Center (US)
  • University of Pennsylvania (US)
Corresponding author
Leach, Steven D.
Venue
Development
Published
2005-08-15
Volume
132
Issue
16
Pages
3767-3776
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W1982781304
Cited by
344
References
39
Citations by year
2026: 7 · 2025: 6 · 2024: 10 · 2023: 17 · 2022: 15 · 2021: 17 · 2020: 14 · 2019: 12 · 2018: 12 · 2017: 14 · 2016: 14 · 2015: 13 · 2014: 24 · 2013: 29 · 2012: 23
FWCI
9.95
Type
journal article
Language
en
Open access
Locations
  • Development (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • American Diabetes Association
  • Vanderbilt University (CA68485)
  • Johns Hopkins University
  • Vanderbilt University Medical Center (CA68485)
  • National Institutes of Health (CA68485, DK 20593)
  • National Cancer Institute (R01CA098322, CA46413, CA-084239, CA68485, F32 CA 76698, U01CA084239, F32CA076698, CA-98322, R01CA046413, P30CA068485)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-58404, DK61215, DK 20593, DK-60694, R01DK061215, P30DK058404, R01DK060694)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
acinar-to-ductal metaplasia, EGFR signaling, pancreatic cancer precursors, lineage tracing, pancreatic development, epithelial metaplasia
MeSH terms
Animals, Cell Differentiation, Epithelium, Gene Expression Regulation, Humans, Intermediate Filament Proteins, Metaplasia, Mice, Transgenic, Nerve Tissue Proteins, Pancreas, Signal Transduction, Transforming Growth Factor alpha, Cell Lineage, Transgenes, Mice, Nestin, ErbB Receptors

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