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In vitro models of medulloblastoma: choosing the right tool for the job

Ivanov, Delyan P.; Coyle, Beth; Walker, David A.; Grabowska, Anna M.

Authors

Delyan P. Ivanov

BETH COYLE BETH.COYLE@NOTTINGHAM.AC.UK
Associate Professor

DAVID WALKER DAVID.WALKER@NOTTINGHAM.AC.UK
Professor of Paediatric Oncology

ANNA GRABOWSKA anna.grabowska@nottingham.ac.uk
Professor of Cancer Microenvironment



Abstract

The recently-defined four molecular subgroups of medulloblastoma have required updating of our understanding of in vitro models to include molecular classification and risk stratification features from clinical practice. This review seeks to build a more comprehensive picture of the in vitro systems available for modelling medulloblastoma.

The subtype classification and molecular characterisation for over 40 medulloblastoma cell-lines has been compiled, making it possible to identify the strengths and weaknesses in current model systems. Less than half (18/44) of established medulloblastoma cell-lines have been subgrouped. The majority of the subgrouped cell-lines (11/18) are Group 3 with MYC-amplification. SHH cell-lines are the next most common (4/18), half of which exhibit TP53 mutation. WNT and Group 4 subgroups, accounting for 50% of patients, remain underrepresented with 1 and 2 cell-lines respectively.

In vitro modelling relies not only on incorporating appropriate tumour cells, but also on using systems with the relevant tissue architecture and phenotype as well as normal tissues. Novel ways of improving the clinical relevance of in vitro models are reviewed, focusing on 3D cell culture, extracellular matrix, co-cultures with normal cells and organotypic slices. This paper champions the establishment of a collaborative online-database and linked cell-bank to catalyse preclinical medulloblastoma research.

Citation

Ivanov, D. P., Coyle, B., Walker, D. A., & Grabowska, A. M. (2016). In vitro models of medulloblastoma: choosing the right tool for the job. Journal of Biotechnology, 236, 10-25. https://doi.org/10.1016/j.jbiotec.2016.07.028

Journal Article Type Article
Acceptance Date Jul 29, 2016
Online Publication Date Aug 3, 2016
Publication Date Oct 20, 2016
Deposit Date Aug 22, 2016
Publicly Available Date Aug 22, 2016
Journal Journal of Biotechnology
Print ISSN 0168-1656
Electronic ISSN 1873-4863
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 236
Pages 10-25
DOI https://doi.org/10.1016/j.jbiotec.2016.07.028
Keywords brain tumor children; cell line molecular subgroups; WNT SHH Group 3 Group 4; three-dimensional cell culture; neurotoxicity testing; normal brain co-culture
Public URL http://eprints.nottingham.ac.uk/id/eprint/35789
Publisher URL http://www.sciencedirect.com/science/article/pii/S0168165616314389
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
Additional Information This article is maintained by: Elsevier; Article Title: In vitro models of medulloblastoma: Choosing the right tool for the job; Journal Title: Journal of Biotechnology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jbiotec.2016.07.028; Content Type: article; Copyright: © 2016 The Author(s). Published by Elsevier B.V.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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