Quantitative in vivo bioluminescence imaging of orthotopic patient-derived glioblastoma xenografts

Koessinger, A. L., Koessinger, D., Stevenson, K., Cloix, C., Mitchell, L., Nixon, C., Gomez-Roman, N. , Chalmers, A. J. , Norman, J. C. and Tait, S. W.G. (2020) Quantitative in vivo bioluminescence imaging of orthotopic patient-derived glioblastoma xenografts. Scientific Reports, 10, 15361. (doi: 10.1038/s41598-020-72322-x) (PMID:32958777) (PMCID:PMC7506024)

Abstract

Despite extensive research, little progress has been made in glioblastoma therapy, owing in part to a lack of adequate preclinical in vivo models to study this disease. To mitigate this, primary patient-derived cell lines, which maintain their specific stem-like phenotypes, have replaced established glioblastoma cell lines. However, due to heterogenous tumour growth inherent in glioblastoma, the use of primary cells for orthotopic in vivo studies often requires large experimental group sizes. Therefore, when using intracranial patient-derived xenograft (PDX) approaches, it is advantageous to deploy imaging techniques to monitor tumour growth and allow stratification of mice. Here we show that stable expression of near-infrared fluorescent protein (iRFP) in patient-derived glioblastoma cells enables rapid, direct non-invasive monitoring of tumour development without compromising tumour stemness or tumorigenicity. Moreover, as this approach does not depend on the use of agents like luciferin, which can cause variability due to changing bioavailability, it can be used for quantitative longitudinal monitoring of tumour growth. Notably, we show that this technique also allows quantitative assessment of tumour burden in highly invasive models spreading throughout the brain. Thus, iRFP transduction of primary patient-derived glioblastoma cells is a reliable, cost- and time-effective way to monitor heterogenous orthotopic PDX growth.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nixon, Mr Colin and Koessinger, Dr Anna and Tait, Professor Stephen and Koessinger, Dr Dominik and Cloix, Dr Catherine and Chalmers, Professor Anthony and Gomez-Roman, Dr Maria and Norman, Professor James and Stevenson, Mrs Katrina and Mitchell, Mrs Louise
• Authors: Koessinger, A. L., Koessinger, D., Stevenson, K., Cloix, C., Mitchell, L., Nixon, C., Gomez-Roman, N., Chalmers, A. J., Norman, J. C., and Tait, S. W.G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Scientific Reports 10:15361
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172007		Apoptosis as an oncogenic process: understanding and exploiting its dark-side	Stephen Tait	Cancer Research UK (CRUK)	C40872/A20145	Institute of Cancer Sciences
172980		CRUK Glasgow Centre Clinical Training Award	Stephen Tait	Cancer Research UK (CRUK)	C596/A23220	Institute of Cancer Sciences
171214		Mitochondrial poisoning as a novel strategy to overcome radiation resistance of glioblastoma	Anthony Chalmers	Chief Scientist Office (CSO)	ETM/405	CS - Clinical Trials Research