A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture
Abstract Bladder cancer is among the most prevalent cancers worldwide. Currently, few bladder cancer models have undergone thorough characterization to assess their fidelity to patient tumors, especially upon propagation in the laboratory. Here, we establish and molecularly characterize CoCaB 1, an...
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2021
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oai:doaj.org-article:5b9f2e7e7f544668b01d526be6457f1a2021-12-02T13:34:57ZA bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture10.1038/s41598-021-83662-72045-2322https://doaj.org/article/5b9f2e7e7f544668b01d526be6457f1a2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83662-7https://doaj.org/toc/2045-2322Abstract Bladder cancer is among the most prevalent cancers worldwide. Currently, few bladder cancer models have undergone thorough characterization to assess their fidelity to patient tumors, especially upon propagation in the laboratory. Here, we establish and molecularly characterize CoCaB 1, an aggressive cisplatin-resistant muscle-invasive bladder cancer patient-derived xenograft (PDX) and companion organoid system. CoCaB 1 was a subcutaneous PDX model reliably transplanted in vivo and demonstrated an acceleration in growth upon serial transplantation, which was reflected in organoid and 2D cell culture systems. Transcriptome analysis revealed progression towards an increasingly proliferative and stem-like expression profile. Gene expression differences between organoid and PDX models reflected expected differences in cellular composition, with organoids enriched in lipid biosynthesis and metabolism genes and deprived of extracellular components observed in PDXs. Both PDX and organoid models maintained the histological fidelity and mutational heterogeneity of their parental tumor. This study establishes the CoCaB 1 PDX and organoid system as companion representative tumor models for the development of novel bladder cancer therapies.Elise Y. CaiJose GarciaYuzhen LiuFunda Vakar-LopezSonali AroraHolly M. NguyenBryce LakelyLisha BrownAlicia WongBruce MontgomeryJohn K. LeeEva CoreyJonathan L. WrightAndrew C. HsiehHung-Ming LamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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Medicine R Science Q Elise Y. Cai Jose Garcia Yuzhen Liu Funda Vakar-Lopez Sonali Arora Holly M. Nguyen Bryce Lakely Lisha Brown Alicia Wong Bruce Montgomery John K. Lee Eva Corey Jonathan L. Wright Andrew C. Hsieh Hung-Ming Lam A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture |
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Abstract Bladder cancer is among the most prevalent cancers worldwide. Currently, few bladder cancer models have undergone thorough characterization to assess their fidelity to patient tumors, especially upon propagation in the laboratory. Here, we establish and molecularly characterize CoCaB 1, an aggressive cisplatin-resistant muscle-invasive bladder cancer patient-derived xenograft (PDX) and companion organoid system. CoCaB 1 was a subcutaneous PDX model reliably transplanted in vivo and demonstrated an acceleration in growth upon serial transplantation, which was reflected in organoid and 2D cell culture systems. Transcriptome analysis revealed progression towards an increasingly proliferative and stem-like expression profile. Gene expression differences between organoid and PDX models reflected expected differences in cellular composition, with organoids enriched in lipid biosynthesis and metabolism genes and deprived of extracellular components observed in PDXs. Both PDX and organoid models maintained the histological fidelity and mutational heterogeneity of their parental tumor. This study establishes the CoCaB 1 PDX and organoid system as companion representative tumor models for the development of novel bladder cancer therapies. |
format |
article |
author |
Elise Y. Cai Jose Garcia Yuzhen Liu Funda Vakar-Lopez Sonali Arora Holly M. Nguyen Bryce Lakely Lisha Brown Alicia Wong Bruce Montgomery John K. Lee Eva Corey Jonathan L. Wright Andrew C. Hsieh Hung-Ming Lam |
author_facet |
Elise Y. Cai Jose Garcia Yuzhen Liu Funda Vakar-Lopez Sonali Arora Holly M. Nguyen Bryce Lakely Lisha Brown Alicia Wong Bruce Montgomery John K. Lee Eva Corey Jonathan L. Wright Andrew C. Hsieh Hung-Ming Lam |
author_sort |
Elise Y. Cai |
title |
A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture |
title_short |
A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture |
title_full |
A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture |
title_fullStr |
A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture |
title_full_unstemmed |
A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture |
title_sort |
bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/5b9f2e7e7f544668b01d526be6457f1a |
work_keys_str_mv |
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