Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses

The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid...

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Autores principales:	A.C. Nickel, D. Picard, N. Qin, M. Wolter, K. Kaulich, M. Hewera, D. Pauck, V. Marquardt, G. Torga, S. Muhammad, W. Zhang, O. Schnell, H.-J. Steiger, D. Hänggi, E. Fritsche, N.-G. Her, D.-H. Nam, M.S. Carro, M. Remke, G. Reifenberger, U.D. Kahlert
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Glioblastoma In vitro drug screening Longitudinal molecular profiling Tumor spheroids Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ef35d0cf9fa94f5e85dbd336eabcbef8
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spelling	oai:doaj.org-article:ef35d0cf9fa94f5e85dbd336eabcbef82021-11-14T04:29:10ZLongitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses0753-332210.1016/j.biopha.2021.112278https://doaj.org/article/ef35d0cf9fa94f5e85dbd336eabcbef82021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010623https://doaj.org/toc/0753-3322The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.A.C. NickelD. PicardN. QinM. WolterK. KaulichM. HeweraD. PauckV. MarquardtG. TorgaS. MuhammadW. ZhangO. SchnellH.-J. SteigerD. HänggiE. FritscheN.-G. HerD.-H. NamM.S. CarroM. RemkeG. ReifenbergerU.D. KahlertElsevierarticleGlioblastomaIn vitro drug screeningLongitudinal molecular profilingTumor spheroidsTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112278- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Glioblastoma In vitro drug screening Longitudinal molecular profiling Tumor spheroids Therapeutics. Pharmacology RM1-950
spellingShingle	Glioblastoma In vitro drug screening Longitudinal molecular profiling Tumor spheroids Therapeutics. Pharmacology RM1-950 A.C. Nickel D. Picard N. Qin M. Wolter K. Kaulich M. Hewera D. Pauck V. Marquardt G. Torga S. Muhammad W. Zhang O. Schnell H.-J. Steiger D. Hänggi E. Fritsche N.-G. Her D.-H. Nam M.S. Carro M. Remke G. Reifenberger U.D. Kahlert Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses
description	The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.
format	article
author	A.C. Nickel D. Picard N. Qin M. Wolter K. Kaulich M. Hewera D. Pauck V. Marquardt G. Torga S. Muhammad W. Zhang O. Schnell H.-J. Steiger D. Hänggi E. Fritsche N.-G. Her D.-H. Nam M.S. Carro M. Remke G. Reifenberger U.D. Kahlert
author_facet	A.C. Nickel D. Picard N. Qin M. Wolter K. Kaulich M. Hewera D. Pauck V. Marquardt G. Torga S. Muhammad W. Zhang O. Schnell H.-J. Steiger D. Hänggi E. Fritsche N.-G. Her D.-H. Nam M.S. Carro M. Remke G. Reifenberger U.D. Kahlert
author_sort	A.C. Nickel
title	Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses
title_short	Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses
title_full	Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses
title_fullStr	Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses
title_full_unstemmed	Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses
title_sort	longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ef35d0cf9fa94f5e85dbd336eabcbef8
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Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses

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