A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses

Gomez-Roman, N. , Stevenson, K., Gilmour, L., Hamilton, G. and Chalmers, A. (2017) A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses. Neuro-Oncology, 19(2), pp. 229-241. (doi:10.1093/neuonc/now164) (PMID:27576873) (PMCID:PMC5463789)

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Abstract

Background. Glioblastoma (GBM) is the most common primary brain tumor, with dismal prognosis. The failure of drug–radiation combinations with promising preclinical data to translate into effective clinical treatments may relate to the use of simplified 2-dimensional in vitro GBM cultures. Methods. We developed a customized 3D GBM culture system based on a polystyrene scaffold (Alvetex) that recapitulates key histological features of GBM and compared it with conventional 2D cultures with respect to their response to radiation and to molecular targeted agents for which clinical data are available. Results. In 3 patient-derived GBM lines, no difference in radiation sensitivity was observed between 2D and 3D cultures, as measured by clonogenic survival. Three different molecular targeted agents, for which robust clinical data are available were evaluated in 2D and 3D conditions: (i) temozolomide, which improves overall survival and is standard of care for GBM, exhibited statistically significant effects on clonogenic survival in both patient-derived cell lines when evaluated in the 3D model compared with only one cell line in 2D cells; (ii) bevacizumab, which has been shown to increase progression-free survival when added to standard chemoradiation in phase III clinical trials, exhibited marked radiosensitizing activity in our 3D model but had no effect on 2D cells; and (iii) erlotinib, which had no efficacy in clinical trials, displayed no activity in our 3D GBM model, but radiosensitized 2D cells. Conclusions. Our 3D model reliably predicted clinical efficacy, strongly supporting its clinical relevance and potential value in preclinical evaluation of drug–radiation combinations for GBM.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hamilton, Dr Graham and Chalmers, Professor Anthony and Gomez-Roman, Dr Maria and Gilmour, Dr Lesley and Stevenson, Mrs Katrina
Authors: Gomez-Roman, N., Stevenson, K., Gilmour, L., Hamilton, G., and Chalmers, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Research Group:Translational Radiation Biology
Journal Name:Neuro-Oncology
Publisher:Oxford Journals
ISSN:1522-8517
ISSN (Online):1523-5866
Published Online:30 August 2016
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Translational Radiation Biology 19(2):229-241
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
677231Mitochondrial poisoning as a novel strategy to overcome radiation resistance of glioblastomaAnthony ChalmersScottish Executive Health Department (SEHHD-CSO)ETM/405ICS - CLINICAL TRIALS RESEARCH
593571Manipulation of cancer cells by nanotopography: strategies to control migration, proliferation and apoptosis (ISSF Catalyst Fund)Penelope TsimbouriWellcome Trust (WELLCOME)097821/Z/11/ZRI MOLECULAR CELL & SYSTEMS BIOLOGY