Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancer
Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer that often displays resistance to conventional cancer therapies, including chemotherapy and radiation therapy. Targeted treatments, including immunotherapies and small molecular inhibitors, have been associated with imp...
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| Format: | Article |
| Language: | English |
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Wiley
2025-07-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.70022 |
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| author | Richard Huang Lynn Kee Alexander Gont Jalna Meens Fraser G. Ferens Meredith S. Irwin Laurie Ailles Scott A. Yuzwa Claire M. Robinson Michael Ohh |
| author_facet | Richard Huang Lynn Kee Alexander Gont Jalna Meens Fraser G. Ferens Meredith S. Irwin Laurie Ailles Scott A. Yuzwa Claire M. Robinson Michael Ohh |
| author_sort | Richard Huang |
| collection | DOAJ |
| description | Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer that often displays resistance to conventional cancer therapies, including chemotherapy and radiation therapy. Targeted treatments, including immunotherapies and small molecular inhibitors, have been associated with improved outcomes. However, variations in the patient response and the development of resistance suggest that more models that better recapitulate the pathogenesis and metastatic mechanisms of ccRCC are required to improve our understanding and disease management. Here, we examined the transcriptional landscapes of in vitro cell culture as well as in vivo orthotopic and metastatic NOD/SCID‐γ mouse models of ccRCC using a single patient‐derived RCC243 cell line to allow unambiguous comparison between models. In our mouse model assays, RCC243 cells formed metastatic tumors, and all tumors retained clear cell morphology irrespective of model type. Notably, gene expression profiles differed markedly between the RCC243 tumor models—cell culture, orthotopic tumors, and metastatic tumors—suggesting an impact of the experimental model system and whether the tumor was orthotopic or metastatic. Furthermore, we found conserved prognostic markers between RCC243 tumor models and human ccRCC patient datasets, and genes upregulated in metastatic RCC243 were associated with worse patient outcomes. |
| format | Article |
| id | doaj-art-b1aa798a1ca64ddbb2727fcb32414518 |
| institution | DOAJ |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-b1aa798a1ca64ddbb2727fcb324145182025-08-20T02:44:28ZengWileyFEBS Open Bio2211-54632025-07-011571124114310.1002/2211-5463.70022Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancerRichard Huang0Lynn Kee1Alexander Gont2Jalna Meens3Fraser G. Ferens4Meredith S. Irwin5Laurie Ailles6Scott A. Yuzwa7Claire M. Robinson8Michael Ohh9Department of Laboratory Medicine and Pathobiology University of Toronto CanadaCell Biology Program The Hospital for Sick Children Toronto CanadaCell Biology Program The Hospital for Sick Children Toronto CanadaPrincess Margaret Cancer Centre University Health Network Toronto CanadaDepartment of Laboratory Medicine and Pathobiology University of Toronto CanadaDepartment of Laboratory Medicine and Pathobiology University of Toronto CanadaPrincess Margaret Cancer Centre University Health Network Toronto CanadaDepartment of Laboratory Medicine and Pathobiology University of Toronto CanadaSchool of Medicine, Health Sciences Centre University College Dublin Dublin 4 IrelandDepartment of Laboratory Medicine and Pathobiology University of Toronto CanadaClear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer that often displays resistance to conventional cancer therapies, including chemotherapy and radiation therapy. Targeted treatments, including immunotherapies and small molecular inhibitors, have been associated with improved outcomes. However, variations in the patient response and the development of resistance suggest that more models that better recapitulate the pathogenesis and metastatic mechanisms of ccRCC are required to improve our understanding and disease management. Here, we examined the transcriptional landscapes of in vitro cell culture as well as in vivo orthotopic and metastatic NOD/SCID‐γ mouse models of ccRCC using a single patient‐derived RCC243 cell line to allow unambiguous comparison between models. In our mouse model assays, RCC243 cells formed metastatic tumors, and all tumors retained clear cell morphology irrespective of model type. Notably, gene expression profiles differed markedly between the RCC243 tumor models—cell culture, orthotopic tumors, and metastatic tumors—suggesting an impact of the experimental model system and whether the tumor was orthotopic or metastatic. Furthermore, we found conserved prognostic markers between RCC243 tumor models and human ccRCC patient datasets, and genes upregulated in metastatic RCC243 were associated with worse patient outcomes.https://doi.org/10.1002/2211-5463.70022animal models of carcinogenesisclear cell renal cell carcinomaIn vitro models of carcinogenesiskidney cancersingle‐cell RNA‐sequencing |
| spellingShingle | Richard Huang Lynn Kee Alexander Gont Jalna Meens Fraser G. Ferens Meredith S. Irwin Laurie Ailles Scott A. Yuzwa Claire M. Robinson Michael Ohh Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancer FEBS Open Bio animal models of carcinogenesis clear cell renal cell carcinoma In vitro models of carcinogenesis kidney cancer single‐cell RNA‐sequencing |
| title | Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancer |
| title_full | Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancer |
| title_fullStr | Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancer |
| title_full_unstemmed | Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancer |
| title_short | Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancer |
| title_sort | comparative single cell transcriptomic profiling of patient derived renal carcinoma cells in cellular and animal models of kidney cancer |
| topic | animal models of carcinogenesis clear cell renal cell carcinoma In vitro models of carcinogenesis kidney cancer single‐cell RNA‐sequencing |
| url | https://doi.org/10.1002/2211-5463.70022 |
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