Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenografts
Abstract Although tumor‐initiating cell (TIC) self‐renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long‐term progression of PDAC in serial xen...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-07-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201607354 |
| _version_ | 1797280517428609024 |
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| author | Claudia R Ball Felix Oppel Karl Roland Ehrenberg Taronish D Dubash Sebastian M Dieter Christopher M Hoffmann Ulrich Abel Friederike Herbst Moritz Koch Jens Werner Frank Bergmann Naveed Ishaque Manfred Schmidt Christof vonKalle Claudia Scholl Stefan Fröhling Benedikt Brors Wilko Weichert Jürgen Weitz Hanno Glimm |
| author_facet | Claudia R Ball Felix Oppel Karl Roland Ehrenberg Taronish D Dubash Sebastian M Dieter Christopher M Hoffmann Ulrich Abel Friederike Herbst Moritz Koch Jens Werner Frank Bergmann Naveed Ishaque Manfred Schmidt Christof vonKalle Claudia Scholl Stefan Fröhling Benedikt Brors Wilko Weichert Jürgen Weitz Hanno Glimm |
| author_sort | Claudia R Ball |
| collection | DOAJ |
| description | Abstract Although tumor‐initiating cell (TIC) self‐renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long‐term progression of PDAC in serial xenotransplantation is driven by a succession of transiently active TICs producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations. An unexpected functional and phenotypic plasticity of pancreatic TICs in vivo underlies the recruitment of inactive TIC clones in serial xenografts. The observed clonal succession of TIC activity in serial xenotransplantation is in stark contrast to the continuous activity of limited numbers of self‐renewing TICs within a fixed cellular hierarchy observed in other epithelial cancers and emphasizes the need to target TIC activation, rather than a fixed TIC population, in PDAC. |
| first_indexed | 2024-03-07T16:41:24Z |
| format | Article |
| id | doaj.art-806e5c3796d448e3a3f8956eba08fa15 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:41:24Z |
| publishDate | 2017-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-806e5c3796d448e3a3f8956eba08fa152024-03-03T08:07:07ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-07-019791893210.15252/emmm.201607354Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenograftsClaudia R Ball0Felix Oppel1Karl Roland Ehrenberg2Taronish D Dubash3Sebastian M Dieter4Christopher M Hoffmann5Ulrich Abel6Friederike Herbst7Moritz Koch8Jens Werner9Frank Bergmann10Naveed Ishaque11Manfred Schmidt12Christof vonKalle13Claudia Scholl14Stefan Fröhling15Benedikt Brors16Wilko Weichert17Jürgen Weitz18Hanno Glimm19Department of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of General Surgery University of Heidelberg Heidelberg GermanyDepartment of General Surgery University of Heidelberg Heidelberg GermanyInstitute of Pathology University Hospital Heidelberg Heidelberg GermanyDivision of Theoretical Bioinformatics German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyDivision of Theoretical Bioinformatics German Cancer Research Center (DKFZ) Heidelberg GermanyGerman Cancer Consortium (DKTK) University of Heidelberg Heidelberg GermanyDepartment of General Surgery University of Heidelberg Heidelberg GermanyDepartment of Translational Oncology National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Heidelberg GermanyAbstract Although tumor‐initiating cell (TIC) self‐renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long‐term progression of PDAC in serial xenotransplantation is driven by a succession of transiently active TICs producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations. An unexpected functional and phenotypic plasticity of pancreatic TICs in vivo underlies the recruitment of inactive TIC clones in serial xenografts. The observed clonal succession of TIC activity in serial xenotransplantation is in stark contrast to the continuous activity of limited numbers of self‐renewing TICs within a fixed cellular hierarchy observed in other epithelial cancers and emphasizes the need to target TIC activation, rather than a fixed TIC population, in PDAC.https://doi.org/10.15252/emmm.201607354clonal dynamicspancreatic cancerphenotypic plasticitytumor‐initiating cells |
| spellingShingle | Claudia R Ball Felix Oppel Karl Roland Ehrenberg Taronish D Dubash Sebastian M Dieter Christopher M Hoffmann Ulrich Abel Friederike Herbst Moritz Koch Jens Werner Frank Bergmann Naveed Ishaque Manfred Schmidt Christof vonKalle Claudia Scholl Stefan Fröhling Benedikt Brors Wilko Weichert Jürgen Weitz Hanno Glimm Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenografts EMBO Molecular Medicine clonal dynamics pancreatic cancer phenotypic plasticity tumor‐initiating cells |
| title | Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenografts |
| title_full | Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenografts |
| title_fullStr | Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenografts |
| title_full_unstemmed | Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenografts |
| title_short | Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenografts |
| title_sort | succession of transiently active tumor initiating cell clones in human pancreatic cancer xenografts |
| topic | clonal dynamics pancreatic cancer phenotypic plasticity tumor‐initiating cells |
| url | https://doi.org/10.15252/emmm.201607354 |
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