Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research
Abstract Patient-derived xenografts (PDXs) provide biologically relevant models and potential platforms for the development of treatment strategies for precision medicine in pancreatic cancer. Furthermore, circulating epithelial tumor cells (CETCs/CTCs) are released into the bloodstream by solid tum...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87054-z |
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| author | Benedikt J. Wagner Andreas Ettner-Sitter Nicolas A. Ihlo Merle Behr Sebastian Koelbl Stefan M. Brunner Florian Weber Bettina M. Rau Hans J. Schlitt Christoph Brochhausen Rebecca Schoenmehl Annalena Artinger Dorothea Schott Monika Pizon Katharina Pachmann Thiha Aung Silke Haerteis Christina Hackl |
| author_facet | Benedikt J. Wagner Andreas Ettner-Sitter Nicolas A. Ihlo Merle Behr Sebastian Koelbl Stefan M. Brunner Florian Weber Bettina M. Rau Hans J. Schlitt Christoph Brochhausen Rebecca Schoenmehl Annalena Artinger Dorothea Schott Monika Pizon Katharina Pachmann Thiha Aung Silke Haerteis Christina Hackl |
| author_sort | Benedikt J. Wagner |
| collection | DOAJ |
| description | Abstract Patient-derived xenografts (PDXs) provide biologically relevant models and potential platforms for the development of treatment strategies for precision medicine in pancreatic cancer. Furthermore, circulating epithelial tumor cells (CETCs/CTCs) are released into the bloodstream by solid tumors and a rare subpopulation—circulating cancer stem cells (cCSCs) – is considered to be responsible for recurrence and plays a key role in metastasis. For the identification of cCSCs, an innovative in vitro assay to generate tumorspheres was established in this study. The number of tumorspheres and CETCs/CTCs was analyzed perioperatively in 25 pancreatic cancer patients. Additionally, an individual in vivo chorioallantoic membrane (CAM) culture system was used to generate PDXs from these tumorspheres. While overall correlations of CETCs/CTCs with clinicopathological parameters did not reach statistical significance, a significant difference in the number of tumorspheres was observed between patient subgroups with lower and higher UICC stages. This finding underscores their potential as biomarkers, providing valuable insights into clinical decision-making and tumor progression. The application of tumorspheres on the CAM successfully established PDXs within 7 days. These xenografts closely resembled the histological features of the primary tumor. Hence, this model represents a novel and fast option for individualized testing of new therapies for PDAC. |
| format | Article |
| id | doaj-art-9a5b6bf00130474098d201bbe1a9c3c9 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-9a5b6bf00130474098d201bbe1a9c3c92025-01-26T12:26:48ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87054-zPatient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer researchBenedikt J. Wagner0Andreas Ettner-Sitter1Nicolas A. Ihlo2Merle Behr3Sebastian Koelbl4Stefan M. Brunner5Florian Weber6Bettina M. Rau7Hans J. Schlitt8Christoph Brochhausen9Rebecca Schoenmehl10Annalena Artinger11Dorothea Schott12Monika Pizon13Katharina Pachmann14Thiha Aung15Silke Haerteis16Christina Hackl17Department of Surgery, University Hospital RegensburgInstitute for Molecular and Cellular Anatomy, University of RegensburgFaculty of Informatics and Data Science, University of RegensburgFaculty of Informatics and Data Science, University of RegensburgTechnology Campus Hutthurm, Deggendorf Institute of TechnologyDepartment of Surgery, University Hospital RegensburgInstitute of Pathology, University of RegensburgDepartment of General, Visceral and Thoracic Surgery, Academic Teaching Hospital NeumarktDepartment of Surgery, University Hospital RegensburgInstitute of Pathology, Medical Faculty Mannheim, Heidelberg UniversityInstitute of Pathology, Medical Faculty Mannheim, Heidelberg UniversityInstitute of Pathology, Medical Faculty Mannheim, Heidelberg UniversitySimfo GmbHSimfo GmbHSimfo GmbHInstitute for Molecular and Cellular Anatomy, University of RegensburgInstitute for Molecular and Cellular Anatomy, University of RegensburgDepartment of Surgery, University Hospital RegensburgAbstract Patient-derived xenografts (PDXs) provide biologically relevant models and potential platforms for the development of treatment strategies for precision medicine in pancreatic cancer. Furthermore, circulating epithelial tumor cells (CETCs/CTCs) are released into the bloodstream by solid tumors and a rare subpopulation—circulating cancer stem cells (cCSCs) – is considered to be responsible for recurrence and plays a key role in metastasis. For the identification of cCSCs, an innovative in vitro assay to generate tumorspheres was established in this study. The number of tumorspheres and CETCs/CTCs was analyzed perioperatively in 25 pancreatic cancer patients. Additionally, an individual in vivo chorioallantoic membrane (CAM) culture system was used to generate PDXs from these tumorspheres. While overall correlations of CETCs/CTCs with clinicopathological parameters did not reach statistical significance, a significant difference in the number of tumorspheres was observed between patient subgroups with lower and higher UICC stages. This finding underscores their potential as biomarkers, providing valuable insights into clinical decision-making and tumor progression. The application of tumorspheres on the CAM successfully established PDXs within 7 days. These xenografts closely resembled the histological features of the primary tumor. Hence, this model represents a novel and fast option for individualized testing of new therapies for PDAC.https://doi.org/10.1038/s41598-025-87054-zPancreatic cancerCancer stem cellChorioallantoic membranePatient-derived xenograftPersonalized medicineLiquid biopsy |
| spellingShingle | Benedikt J. Wagner Andreas Ettner-Sitter Nicolas A. Ihlo Merle Behr Sebastian Koelbl Stefan M. Brunner Florian Weber Bettina M. Rau Hans J. Schlitt Christoph Brochhausen Rebecca Schoenmehl Annalena Artinger Dorothea Schott Monika Pizon Katharina Pachmann Thiha Aung Silke Haerteis Christina Hackl Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research Scientific Reports Pancreatic cancer Cancer stem cell Chorioallantoic membrane Patient-derived xenograft Personalized medicine Liquid biopsy |
| title | Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research |
| title_full | Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research |
| title_fullStr | Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research |
| title_full_unstemmed | Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research |
| title_short | Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research |
| title_sort | patient derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research |
| topic | Pancreatic cancer Cancer stem cell Chorioallantoic membrane Patient-derived xenograft Personalized medicine Liquid biopsy |
| url | https://doi.org/10.1038/s41598-025-87054-z |
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