EMT and Dissemination Precede Pancreatic Tumor Formation
Open accessAbstract
Metastasis is the leading cause of cancer-associated death but has been difficult to study because it involves a series of rare, stochastic events. To capture these events, we developed a sensitive method to tag and track pancreatic epithelial cells in a mouse model of pancreatic cancer. Tagged cells invaded and entered the bloodstream unexpectedly early, before frank malignancy could be detected by rigorous histologic analysis; this behavior was widely associated with epithelial-to-mesenchymal transition (EMT). Circulating pancreatic cells maintained a mesenchymal phenotype, exhibited stem cell properties, and seeded the liver. EMT and invasiveness were most abundant at inflammatory foci, and induction of pancreatitis increased the number of circulating pancreatic cells. Conversely, treatment with the immunosuppressive agent dexamethasone abolished dissemination. These results provide insight into the earliest events of cellular invasion in situ and suggest that inflammation enhances cancer progression in part by facilitating EMT and entry into the circulation.
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Preclinical studies show that disseminated PDAC cells can be detected in circulation before localized invasion is visible in primary tumors.
“pre-clinical studies have demonstrated that disseminated PDAC cells can be observed in circulation before localized invasion is readily visualized in primary tumors12.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [12]
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- Authors
- Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F., Reichert, M., Beatty, G. L., Rustgi, A. K., Vonderheide, R. H., Leach, S. D., & Stanger, B. Z.
- Affiliations
- Abramson Cancer Center (US)
- Johns Hopkins University (US)
- Corresponding author
- Stanger, Ben Z.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 148
- Issue
- 1-2
- Pages
- 349-361
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3266542
- OpenAlex
- W2019214567
- Cited by
- 2,136
- References
- 47
- Citations by year
- 2026: 90 · 2025: 109 · 2024: 128 · 2023: 130 · 2022: 152 · 2021: 163 · 2020: 166 · 2019: 198 · 2018: 159 · 2017: 182 · 2016: 186 · 2015: 158 · 2014: 122 · 2013: 127 · 2012: 65
- FWCI
- 74.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 563 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P01CA134292, K08CA138907, CA117969, CA138907, L30 CA136450, CA134292, P01CA117969)
- National Institute of General Medical Sciences (T32GM066691)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK083111, K08DK088945, T32DK007066, DK007066, DK088945, DK083111, P30 DK 19525, R01DK083355, DK083355, P30DK019525, P30DK050306)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- pancreatic cancer, epithelial-mesenchymal transition, metastasis, pancreatic epithelial cells, cell tracking, circulating tumor cells, liver metastasis, pancreatitis, inflammation, dexamethasone, immunosuppression, cancer stem cells, tumor invasion, mouse model
- MeSH terms
- Animals, Disease Models, Animal, Humans, Neoplasm Invasiveness, Pancreatic Neoplasms, Pancreatitis, Neoplastic Stem Cells, Carcinoma, Pancreatic Ductal, Mice, Epithelial-Mesenchymal Transition
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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