Vollständiger Abstract
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Abstract Pancreatic intraepithelial neoplasia (PanIN) precedes pancreatic cancer, a deadly disease characterized by an extensive tumor microenvironment. How the microenvironment evolves during cancer progression is largely unknown, as PanINs are microscopic and nondiseased pancreas samples are exceedingly rare, while adjacent normal samples are disrupted by the presence of malignancy. Leveraging donor organs and spatial technologies, we mapped the evolution of PanIN to cancer. The PanIN epithelial component falls on a continuum with cancer, whereas the PanIN microenvironment is drastically distinct. Progression to cancer is accompanied by profound geographic reorganization of myeloid cells and lymphocytes and the formation of a cancer-specific fibroblast population characterized by high levels of smooth muscle actin, LRRC15, and the WNT signaling component LEF1. Together, our data show asynchronous evolution of epithelial and stromal components during pancreatic carcinogenesis. Lack of stromal reprogramming might explain why most PanINs do not progress to cancer. Compiled data available at https://www.pancreas-precancer-atlas.com/. Significance: Pancreatic cancer precursor lesions are widely prevalent in the population, but progression to invasive cancer is uncommon. Identifying barriers to cancer progression is critical for cancer interception. Our findings describe unique features of the precancer microenvironment that are likely responsible for keeping precursor lesions from progressing to malignancy.
Bibliografischer Nachweis
Publikationsdaten
- Autor:innen
- Ahmed M. Elhossiny, Padma Kadiyala, Jude O. Okoye, Harrison L. Hiraki, Megan C. Procario, Thejaswini Giridharan, Hannah R. Watkoske, Mariana Tannus Ruckert, Jiayue Wang, Brian D. Griffith, Alexander W. Bray, Jamie N. Mills, Carlos E. Espinoza, Jörg Zeller, Nicole Peterson, Filip Bednar, Yaqing Zhang, Arvind Rao, Costas A. Lyssiotis, Julianne M. Szczepanski, Jiaqi Shi, Atul Deshpande, Anirban Maitra, Elana J. Fertig, Eileen S. Carpenter, Timothy L. Frankel, Marina Pasca di Magliano
- Quelle
- Cancer Discovery
- Publikation
- 2026-01-01
- Band / Ausgabe
- Nicht angegeben
- Seiten
- Nicht angegeben
- ISSN / ISBN
- 2159-8274, 2159-8290
- Zitationen
- 1 laut Crossref
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Zitierfähiger Nachweis
Ahmed M. Elhossiny, Padma Kadiyala, Jude O. Okoye, Harrison L. Hiraki, Megan C. Procario, Thejaswini Giridharan, Hannah R. Watkoske, Mariana Tannus Ruckert, Jiayue Wang, Brian D. Griffith, Alexander W. Bray, Jamie N. Mills, Carlos E. Espinoza, Jörg Zeller, Nicole Peterson, Filip Bednar, Yaqing Zhang, Arvind Rao, Costas A. Lyssiotis, Julianne M. Szczepanski, Jiaqi Shi, Atul Deshpande, Anirban Maitra, Elana J. Fertig, Eileen S. Carpenter, Timothy L. Frankel, Marina Pasca di Magliano (2026). Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-25-2001
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