Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice

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  • dc.contributor.author Cáceres, Marta
  • dc.contributor.author Quesada Diez, Rita
  • dc.contributor.author Iglesias, Mar
  • dc.contributor.author Real, Francisco X.
  • dc.contributor.author Villamonte, Maria
  • dc.contributor.author Martínez de Villarreal, Jaime
  • dc.contributor.author Pérez, Mónica
  • dc.contributor.author Andaluz, Anna
  • dc.contributor.author Moll, Xavier
  • dc.contributor.author Berjano, Enrique J.
  • dc.contributor.author Dorcaratto, Dimitri
  • dc.contributor.author Sánchez Velázquez, Patricia, 1985-
  • dc.contributor.author Grande Posa, Luís
  • dc.contributor.author Burdío Pinilla, Fernando
  • dc.date.accessioned 2020-12-15T08:07:56Z
  • dc.date.available 2020-12-15T08:07:56Z
  • dc.date.issued 2020
  • dc.description.abstract Pancreatic duct ligation (PDL) in the murine model has been described as an exocrine pancreatic atrophy-inducing procedure. However, its influence has scarcely been described on premalignant lesions. This study describes the histological changes of premalignant lesions and the gene expression in a well-defined model of pancreatic ductal adenocarcinoma by PDL. Selective ligation of the splenic lobe of the pancreas was performed in Ptf1a-Cre(+/ki); K-ras LSLG12Vgeo(+/ki) mice (PDL-Kras mice). Three experimental groups were evaluated: PDL group, controls and shams. The presence and number of premalignant lesions (PanIN 1-3 and Atypical Flat Lesions-AFL) in proximal (PP) and distal (DP) pancreas were studied for each group over time. Microarray analysis was performed to find differentially expressed genes (DEG) between PP and PD. Clinical human specimens after pancreaticoduodenectomy with ductal occlusion were also evaluated. PDL-Kras mice showed an intense pattern of atrophy in DP which was shrunk to a minimal portion of tissue. Mice in control and sham groups had a 7 and 10-time increase respectively of risk of high-grade PanIN 2 and 3 and AFL in their DP than PDL-Kras mice. Furthermore, PDL-Kras mice had significantly less PanIN 1 and 2 and AFL lesions in DP compared to PP. We identified 38 DEGs comparing PP and PD. Among them, several mapped to protein secretion and digestion while others such as Nupr1 have been previously associated with PanIN and PDAC. PDL in Ptf1a-Cre(+/ki); K-ras LSLG12Vgeo(+/ki) mice induces a decrease in the presence of premalignant lesions in the ligated DP. This could be a potential line of research of interest in some cancerous risk patients.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Cáceres M, Quesada R, Iglesias M, Real FX, Villamonte M, de Villarreal JM, Pérez M, Andaluz A, Moll X, Berjano E, Dorcaratto D, Velazquez PS, Grande L, Burdío F. Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice. Sci Rep. 2020; 10(1):18344. DOI: 10.1038/s41598-020-74947-4
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-020-74947-4
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/46040
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Sci Rep. 2020; 10(1):18344
  • dc.rights © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Cancer
  • dc.subject.keyword Diseases
  • dc.subject.keyword Medical research
  • dc.subject.keyword Pathogenesis
  • dc.title Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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