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

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

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: https://nottingham-repository.worktribe.com/output/822380
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0168165616314389
• 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.
• Contract Date: Aug 22, 2016