Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines
There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients’ response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vul...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13530 |
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| author | Feng Guo Kejia Kan Felix Rückert Wolfgang Rückert Lin Li Johannes Eberhard Tobias May Carsten Sticht Wilhelm G. Dirks Christoph Reißfelder Prama Pallavi Michael Keese |
| author_facet | Feng Guo Kejia Kan Felix Rückert Wolfgang Rückert Lin Li Johannes Eberhard Tobias May Carsten Sticht Wilhelm G. Dirks Christoph Reißfelder Prama Pallavi Michael Keese |
| author_sort | Feng Guo |
| collection | DOAJ |
| description | There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients’ response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial–mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening. |
| first_indexed | 2024-03-10T23:20:41Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:20:41Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-958386464ae94330950a5f1ba0470c832023-11-19T08:18:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171353010.3390/ijms241713530Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell LinesFeng Guo0Kejia Kan1Felix Rückert2Wolfgang Rückert3Lin Li4Johannes Eberhard5Tobias May6Carsten Sticht7Wilhelm G. Dirks8Christoph Reißfelder9Prama Pallavi10Michael Keese11Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanySurgical Department, Diakonissen Krankenhaus Speyer, 67346 Speyer, GermanyIngenieurbüro Dr. Ing. Rückert Data Analysis, Kirchweg 4, 57647 Nistertal, GermanyDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyInSCREENeX GmbH, Inhoffenstr. 7, 38124 Braunschweig, GermanyNext Generation Sequencing Core Facility, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyLeibniz Institute DSMZ, German Collection of Microorganisms and Cell Cultures GmbH, Inhoffenstraße 7B, 38124 Braunschweig, GermanyDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyDepartment of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyEuropean Center of Angioscience ECAS, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyThere is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients’ response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial–mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening.https://www.mdpi.com/1422-0067/24/17/13530chemosensitivityRNA-Seqpatient-tailored therapychemotherapyregression analysisstatistical comparison of populations |
| spellingShingle | Feng Guo Kejia Kan Felix Rückert Wolfgang Rückert Lin Li Johannes Eberhard Tobias May Carsten Sticht Wilhelm G. Dirks Christoph Reißfelder Prama Pallavi Michael Keese Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines International Journal of Molecular Sciences chemosensitivity RNA-Seq patient-tailored therapy chemotherapy regression analysis statistical comparison of populations |
| title | Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines |
| title_full | Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines |
| title_fullStr | Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines |
| title_full_unstemmed | Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines |
| title_short | Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines |
| title_sort | comparison of tumour specific phenotypes in human primary and expandable pancreatic cancer cell lines |
| topic | chemosensitivity RNA-Seq patient-tailored therapy chemotherapy regression analysis statistical comparison of populations |
| url | https://www.mdpi.com/1422-0067/24/17/13530 |
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