3D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, partly due to the dense desmoplasia and a lack of suitable model systems to study. In the present work, we developed a 3D heterospecies spheroid model to study the microenvironmental interactions between tumor cells and...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-07-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523321000991 |
| _version_ | 1818600344258609152 |
|---|---|
| author | Xinyuan Liu Beate Gündel Xidan Li Jianping Liu Anthony Wright Matthias Löhr Gustav Arvidsson Rainer Heuchel |
| author_facet | Xinyuan Liu Beate Gündel Xidan Li Jianping Liu Anthony Wright Matthias Löhr Gustav Arvidsson Rainer Heuchel |
| author_sort | Xinyuan Liu |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, partly due to the dense desmoplasia and a lack of suitable model systems to study. In the present work, we developed a 3D heterospecies spheroid model to study the microenvironmental interactions between tumor cells and stellate cells which can also be employed to test therapeutic regimens. We set up monospheroids and heterospheroids made up from murine pancreatic stellate cells (mPSCs) and human PDAC cells (Panc1), which allowed for direct isolation of mRNA from a mixed cell population followed by an in silico separation of the RNA-seq reads. Global transcript level changes for cells in heterospheroids versus monospheroids were calculated, followed by gene set enrichment analysis and molecular subtype analysis. We observed an apparent shift of Panc1 from the classical to the squamous/basal-like phenotype upon co-culture with mPSCs. Moreover, mPSCs acquired a different cancer-associated fibroblast-related phenotype upon co-culture with Panc1. We analyzed the tumor cell-specific chemosensitivities towards gemcitabine, paclitaxel and SN38 and compared these to published pharmacotranscriptomic signatures. In conclusion, our heterospecies spheroid model reflected key aspects of PDAC and facilitated the study of intercellular interactions between tumor and stroma while additionally proving to be a good model for studying therapeutic responses. |
| first_indexed | 2024-12-16T12:34:00Z |
| format | Article |
| id | doaj.art-15f198d3d0964cc085088e9a0ad7945e |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-16T12:34:00Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-15f198d3d0964cc085088e9a0ad7945e2022-12-21T22:31:38ZengElsevierTranslational Oncology1936-52332021-07-011471011073D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinomaXinyuan Liu0Beate Gündel1Xidan Li2Jianping Liu3Anthony Wright4Matthias Löhr5Gustav Arvidsson6Rainer Heuchel7Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, Huddinge SE 141 86, SwedenPancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, Huddinge SE 141 86, SwedenDepartment of Medicine, Karolinska Institutet, Huddinge SE 141 86, SwedenDepartment of Medicine, Karolinska Institutet, Huddinge SE 141 86, SwedenDivision of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Huddinge SE 141 86, SwedenPancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, Huddinge SE 141 86, SwedenDivision of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Huddinge SE 141 86, SwedenPancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, Huddinge SE 141 86, Sweden; Corresponding author.Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, partly due to the dense desmoplasia and a lack of suitable model systems to study. In the present work, we developed a 3D heterospecies spheroid model to study the microenvironmental interactions between tumor cells and stellate cells which can also be employed to test therapeutic regimens. We set up monospheroids and heterospheroids made up from murine pancreatic stellate cells (mPSCs) and human PDAC cells (Panc1), which allowed for direct isolation of mRNA from a mixed cell population followed by an in silico separation of the RNA-seq reads. Global transcript level changes for cells in heterospheroids versus monospheroids were calculated, followed by gene set enrichment analysis and molecular subtype analysis. We observed an apparent shift of Panc1 from the classical to the squamous/basal-like phenotype upon co-culture with mPSCs. Moreover, mPSCs acquired a different cancer-associated fibroblast-related phenotype upon co-culture with Panc1. We analyzed the tumor cell-specific chemosensitivities towards gemcitabine, paclitaxel and SN38 and compared these to published pharmacotranscriptomic signatures. In conclusion, our heterospecies spheroid model reflected key aspects of PDAC and facilitated the study of intercellular interactions between tumor and stroma while additionally proving to be a good model for studying therapeutic responses.http://www.sciencedirect.com/science/article/pii/S1936523321000991Pancreatic cancerCancer associated fibroblastsCo-cultureSpheroidsTumor microenvironment |
| spellingShingle | Xinyuan Liu Beate Gündel Xidan Li Jianping Liu Anthony Wright Matthias Löhr Gustav Arvidsson Rainer Heuchel 3D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma Translational Oncology Pancreatic cancer Cancer associated fibroblasts Co-culture Spheroids Tumor microenvironment |
| title | 3D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma |
| title_full | 3D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma |
| title_fullStr | 3D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma |
| title_full_unstemmed | 3D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma |
| title_short | 3D heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma |
| title_sort | 3d heterospecies spheroids of pancreatic stroma and cancer cells demonstrate key phenotypes of pancreatic ductal adenocarcinoma |
| topic | Pancreatic cancer Cancer associated fibroblasts Co-culture Spheroids Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S1936523321000991 |
| work_keys_str_mv | AT xinyuanliu 3dheterospeciesspheroidsofpancreaticstromaandcancercellsdemonstratekeyphenotypesofpancreaticductaladenocarcinoma AT beategundel 3dheterospeciesspheroidsofpancreaticstromaandcancercellsdemonstratekeyphenotypesofpancreaticductaladenocarcinoma AT xidanli 3dheterospeciesspheroidsofpancreaticstromaandcancercellsdemonstratekeyphenotypesofpancreaticductaladenocarcinoma AT jianpingliu 3dheterospeciesspheroidsofpancreaticstromaandcancercellsdemonstratekeyphenotypesofpancreaticductaladenocarcinoma AT anthonywright 3dheterospeciesspheroidsofpancreaticstromaandcancercellsdemonstratekeyphenotypesofpancreaticductaladenocarcinoma AT matthiaslohr 3dheterospeciesspheroidsofpancreaticstromaandcancercellsdemonstratekeyphenotypesofpancreaticductaladenocarcinoma AT gustavarvidsson 3dheterospeciesspheroidsofpancreaticstromaandcancercellsdemonstratekeyphenotypesofpancreaticductaladenocarcinoma AT rainerheuchel 3dheterospeciesspheroidsofpancreaticstromaandcancercellsdemonstratekeyphenotypesofpancreaticductaladenocarcinoma |