Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery.
Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA c...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003954 |
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| author | Sharada Mokkapati Ganiraju Manyam Alexis R. Steinmetz Côme Tholomier Alberto Martini Woonyoung Choi Bogdon Czerniak Byron H Lee Colin P Dinney David J McConkey |
| author_facet | Sharada Mokkapati Ganiraju Manyam Alexis R. Steinmetz Côme Tholomier Alberto Martini Woonyoung Choi Bogdon Czerniak Byron H Lee Colin P Dinney David J McConkey |
| author_sort | Sharada Mokkapati |
| collection | DOAJ |
| description | Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models. Patient-derived, luciferase-tagged BLCA cell lines were cultured in vitro and engrafted into bladders of NSG mice. Tumor growth was monitored using bioluminescence imaging and mRNA-based molecular classification was used to characterize xenografts into molecular subtypes. RNAseq analysis and basal, luminal, and epithelial-mesenchymal transition (EMT) marker expression revealed distinct patterns; certain cell lines expressed predominantly basal or luminal markers while others demonstrated mixed expression. SCaBER expressed high basal and EMT markers and low luminal markers, consistent with a true basal cell. RT4V6 was a true luminal cell line, displaying only high luminal makers. UC13, T24 and UC3 only showed increased expression of EMT markers. RT112, UC6, UC9 and UC14 expressed basal, luminal, and EMT markers. Immunohistochemical analysis validated our findings. Ki67 was assessed as a continuous percentage of positively stained cells. Morphological assessment of xenografts included H&E and α-SMA staining. These findings will allow for the rational use of appropriate models to develop targeted therapies to overcome or manipulate mechanisms of treatment resistance in BLCA. |
| format | Article |
| id | doaj-art-0b4fd47b36f64f1783afca8e6101bf87 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-0b4fd47b36f64f1783afca8e6101bf872025-01-22T05:41:34ZengElsevierTranslational Oncology1936-52332025-02-0152102269Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery.Sharada Mokkapati0Ganiraju Manyam1Alexis R. Steinmetz2Côme Tholomier3Alberto Martini4Woonyoung Choi5Bogdon Czerniak6Byron H Lee7Colin P Dinney8David J McConkey9Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Correspondence author at: Urology. University of Texas MD Anderson Cancer Center, 7777 Knight Rd, Smith Research Building, Houston, Texas, 77584.Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAJohns Hopkins Greenberg Bladder Cancer Institute, Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USADepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAJohns Hopkins Greenberg Bladder Cancer Institute, Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA; Correspondence author at: Greenberg Bladder Cancer Institute, John Hopkins University, 600 N Wolfe St. Baltimore, MD, 21287.Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models. Patient-derived, luciferase-tagged BLCA cell lines were cultured in vitro and engrafted into bladders of NSG mice. Tumor growth was monitored using bioluminescence imaging and mRNA-based molecular classification was used to characterize xenografts into molecular subtypes. RNAseq analysis and basal, luminal, and epithelial-mesenchymal transition (EMT) marker expression revealed distinct patterns; certain cell lines expressed predominantly basal or luminal markers while others demonstrated mixed expression. SCaBER expressed high basal and EMT markers and low luminal markers, consistent with a true basal cell. RT4V6 was a true luminal cell line, displaying only high luminal makers. UC13, T24 and UC3 only showed increased expression of EMT markers. RT112, UC6, UC9 and UC14 expressed basal, luminal, and EMT markers. Immunohistochemical analysis validated our findings. Ki67 was assessed as a continuous percentage of positively stained cells. Morphological assessment of xenografts included H&E and α-SMA staining. These findings will allow for the rational use of appropriate models to develop targeted therapies to overcome or manipulate mechanisms of treatment resistance in BLCA.http://www.sciencedirect.com/science/article/pii/S1936523324003954Bladder cancerMolecular subtypes of bladder cancerTranscriptomic classifierLuminalBasal |
| spellingShingle | Sharada Mokkapati Ganiraju Manyam Alexis R. Steinmetz Côme Tholomier Alberto Martini Woonyoung Choi Bogdon Czerniak Byron H Lee Colin P Dinney David J McConkey Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery. Translational Oncology Bladder cancer Molecular subtypes of bladder cancer Transcriptomic classifier Luminal Basal |
| title | Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery. |
| title_full | Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery. |
| title_fullStr | Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery. |
| title_full_unstemmed | Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery. |
| title_short | Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery. |
| title_sort | molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery |
| topic | Bladder cancer Molecular subtypes of bladder cancer Transcriptomic classifier Luminal Basal |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003954 |
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