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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Autores principales: 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
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/5b9f2e7e7f544668b01d526be6457f1a
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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
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