Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice
Cáceres, Marta (Hospital del Mar (Barcelona, Catalunya))
Quesada, Rita (Hospital del Mar (Barcelona, Catalunya))
Iglesias, Mar (Hospital del Mar (Barcelona, Catalunya))
Real, Francisco X. (Centro Nacional de Investigaciones Oncológicas)
Villamonte, Maria (Hospital del Mar (Barcelona, Catalunya))
de Villarreal, Jaime Martinez (Centro Nacional de Investigaciones Oncológicas)
Pérez, Mónica (Centro Nacional de Investigaciones Oncológicas)
Andaluz Martínez, Anna (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Moll Sánchez, Xavier (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Berjano, Enrique (Universitat Politècnica de València. Departament d'Enginyeria Electrònica)
Dorcaratto, Dimitri (Hospital Clínic Universitari (València))
Velazquez, Patricia Sánchez (Hospital del Mar (Barcelona, Catalunya))
Grande, L (Hospital del Mar (Barcelona, Catalunya))
Burdío, Fernando (Hospital del Mar (Barcelona, Catalunya))

Data:	2020
Resum:	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.
Ajuts:	Ministerio de Economía, Industria y Competitividad RTI2018-094357-B-C22
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cancer ; Diseases ; Medical research ; Pathogenesis
Publicat a:	Scientific reports, Vol. 10 (october 2020) , ISSN 2045-2322

DOI: 10.1038/s41598-020-74947-4
PMID: 33110094

12 p, 2.8 MB

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